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51.
Santos RL Wajid M Khan MN McArthur N Pham TL Bhatti A Lee K Irshad S Mir A Yan K Chahrour MH Ansar M Ahmad W Leal SM 《Human mutation》2005,26(4):396
Though many hearing impairment genes have been identified, only a few of these genes have been screened in population studies. For this study, 168 Pakistani families with autosomal recessive hearing impairment not due to mutations in the GJB2 (Cx26) gene underwent a genome scan. Two-point and multipoint parametric linkage analyses were carried out. Twelve families had two-point or multipoint LOD scores of 1.4 or greater within the transmembrane cochlear expressed gene 1 (TMC1) region and were subjected to further screening with direct DNA sequencing. Five novel putatively functional non-synonymous sequence variants, c.830A>G (p.Y277C), c.1114G>A (p.V372M), c.1334G>A (p.R445H), c.2004T>G (p.S668R), and c.2035G>A (p.E679K), were found to segregate within seven families, but were not observed in 234 Pakistani control chromosomes. The variants c.830A>G (p.Y277C), c.1114G>A (p.V372M), and c.1334G>A (p.R445H) occurred at highly conserved regions and were predicted to lie within hydrophobic transmembrane domains, while non-synonymous variants c.2004T>G (p.S668R) and c.2035G>A (p.E679K) occurred in extracellular regions that were not highly conserved. There is evidence that the c.2004T>G (p.S668R) variant may have occurred at a phosphorylation site. One family has the known splice site mutation c.536 -8T>A. The prevalence of non-syndromic hearing impairment due to TMC1 in this Pakistani population is 4.4% (95%CI: 1.9, 8.6%). The TMC1 protein might have an important function in K(+) channels of inner hair cells, which would be consistent with the hypothetical structure of protein domains in which sequence variants were identified. 相似文献
52.
There is now considerable evidence suggesting that the plasma membrane of mammalian cells is compartmentalized by functional lipid raft microdomains. These structures are assemblies of specialized lipids and proteins and have been implicated in diverse biological functions. Analysis of their protein content using proteomics and other methods revealed enrichment of signalling proteins, suggesting a role for these domains in intracellular signalling. In T lymphocytes, structure/function experiments and complementary pharmacological studies have shown that raft microdomains control the localization and function of proteins which are components of signalling pathways regulated by the T-cell antigen receptor (TCR). Based on these studies, a model for TCR phosphorylation in lipid rafts is presented. However, despite substantial progress in the field, critical questions remain. For example, it is unclear if membrane rafts represent a homogeneous population and if their structure is modified upon TCR stimulation. In the future, proteomics and the parallel development of complementary analytical methods will undoubtedly contribute in further delineating the role of lipid rafts in signal transduction mechanisms. 相似文献
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54.
The increasing prevalence of penicillin-resistant Streptococuus pneumoniae urges for fast and accurate susceptibility testing methods. This study evaluated the comparability of three commonly used techniques; disk diffusion, E-test and agar dilution, to detect penicillin susceptibility in clinical isolates of S. pneumoniae. Fifty pneumococcal isolates, obtained from patients at the University of Malaya Medical Centre, were selected to include both penicillin-susceptible strains and those that had decreased susceptibility (resistant and intermediate) to penicillin. The minimum inhibitory concentration (MIC) values of penicillin to serve as the reference was determined by the agar dilution method in which, based on the MIC breakpoints recommended by the National Committee for Clinical Laboratory Standards (NCCLS), 27 strains had decreased susceptibility to penicillin with 17 strains resistant and 10 intermediate. Comparing to the agar dilution method, oxacillin disk diffusion test detected all strains with decreased penicillin susceptibility as such while E-test showed a close agreement of susceptibility (92%) of the isolates to penicillin. This confirmed that oxacillin is a good screening test for S. pneumoniae isolates with decreased susceptibility to penicillin while E-test is very reliable for rapid and accurate detection of penicillin susceptibility. 相似文献
55.
Hashaam Akhtar Samar Akhtar Fazal-Ul Rahman Maham Afridi Sundas Khalid Sabahat Ali Nasim Akhtar Yousef S Khader Hamaad Ahmad Muhammad Mujeeb Khan 《JMIR Public Health and Surveillance》2021,7(5)
BackgroundSince the first reports of COVID-19 infection, the foremost requirement has been to identify a treatment regimen that not only fights the causative agent but also controls the associated complications of the infection. Due to the time-consuming process of drug discovery, physicians have used readily available drugs and therapies for treatment of infections to minimize the death toll.ObjectiveThe aim of this study is to provide a snapshot analysis of the major drugs used in a cohort of 1562 Pakistani patients during the period from May to July 2020, when the first wave of COVID-19 peaked in Pakistan.MethodsA retrospective observational study was performed to provide an overview of the major drugs used in a cohort of 1562 patients with COVID-19 admitted to the four major tertiary-care hospitals in the Rawalpindi-Islamabad region of Pakistan during the peak of the first wave of COVID-19 in the country (May-July 2020).ResultsAntibiotics were the most common choice out of all the therapies employed, and they were used as first line of treatment for COVID-19. Azithromycin was the most prescribed drug for treatment. No monthly trend was observed in the choice of antibiotics, and these drugs appeared to be a random but favored choice throughout the months of the study. It was also noted that even antibiotics used for multidrug resistant infections were prescribed irrespective of the severity or progression of the infection. The results of the analysis are alarming, as this approach may lead to antibiotic resistance and complications in immunocompromised patients with COVID-19. A total of 1562 patients (1064 male, 68.1%, and 498 female, 31.9%) with a mean age of 47.35 years (SD 17.03) were included in the study. The highest frequency of patient hospitalizations occurred in June (846/1562, 54.2%).ConclusionsGuidelines for a targeted treatment regime are needed to control related complications and to limit the misuse of antibiotics in the management of COVID-19. 相似文献
56.
Munaza Fatima Santosh Kumar Mudassar Hussain Naveed Masood Memon Anum Vighio Muhammad Asif Syed Ambreen Chaudhry Zakir Hussain Zeeshan Iqbal Baig Mirza Amir Baig Rana Jawad Asghar Aamer Ikram Yousef Khader 《JMIR Public Health and Surveillance》2021,7(5)
BackgroundHyderabad, Pakistan, was the first city to witness an outbreak of extensively drug resistant (XDR) typhoid fever. The outbreak strain is resistant to ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, fluoroquinolones, and third-generation cephalosporin, thus greatly limiting treatment options. However, despite over 5000 documented cases, information on mortality and morbidity has been limited.ObjectiveTo address the existing knowledge gap, this study aimed to assess the morbidity and mortality associated with XDR and non-XDR Salmonella serovar Typhi infections in Pakistan.MethodsWe reviewed the medical records of culture-confirmed typhoid cases in 5 hospitals in Hyderabad from October 1, 2016, to September 30, 2018. We recorded data on age, gender, onset of fever, physical examination, serological and microbiological test results, treatment before and during hospitalization, duration of hospitalization, complications, and deaths.ResultsA total of 1452 culture-confirmed typhoid cases, including 947 (66%) XDR typhoid cases and 505 (34%) non-XDR typhoid cases, were identified. Overall, ≥1 complications were reported in 360 (38%) patients with XDR typhoid and 89 (18%) patients with non-XDR typhoid (P<.001). Ileal perforation was the most commonly reported complication in both patients with XDR typhoid (n=210, 23%) and patients with non-XDR typhoid (n=71, 14%) (P<.001). Overall, mortality was documented among 17 (1.8%) patients with XDR S Typhi infections and 3 (0.6%) patients with non-XDR S Typhi infections (P=.06).ConclusionsAs this first XDR typhoid outbreak continues to spread, the increased duration of illness before hospitalization and increased rate of complications have important implications for clinical care and medical costs and heighten the importance of prevention and control measures. 相似文献
57.
Dalia Khoury Alexander Preiss Paul Geiger Mohd Anwar Kevin Paul Conway 《JMIR Public Health and Surveillance》2021,7(5)
BackgroundThe opioid crisis in the United States may be exacerbated by the COVID-19 pandemic. Increases in opioid use, emergency medical services (EMS) runs for opioid-related overdoses, and opioid overdose deaths have been reported. No study has examined changes in multiple naloxone administrations, an indicator of overdose severity, during the COVID-19 pandemic.ObjectiveThis study examines changes in the occurrence of naloxone administrations and multiple naloxone administrations during EMS runs for opioid-related overdoses during the COVID-19 pandemic in Guilford County, North Carolina (NC).MethodsUsing a period-over-period approach, we compared the occurrence of opioid-related EMS runs, naloxone administrations, and multiple naloxone administrations during the 29-week period before (September 1, 2019, to March 9, 2020) and after NC’s COVID-19 state of emergency declaration (ie, the COVID-19 period of March 10 to September 30, 2020). Furthermore, historical data were used to generate a quasi-control distribution of period-over-period changes to compare the occurrence of each outcome during the COVID-19 period to each 29-week period back to January 1, 2014.ResultsAll outcomes increased during the COVID-19 period. Compared to the previous 29 weeks, the COVID-19 period experienced increases in the weekly mean number of opioid-related EMS runs (25.6, SD 5.6 vs 18.6, SD 6.6; P<.001), naloxone administrations (22.3, SD 6.2 vs 14.1, SD 6.0; P<.001), and multiple naloxone administrations (5.0, SD 1.9 vs 2.7, SD 1.9; P<.001), corresponding to proportional increases of 37.4%, 57.8%, and 84.8%, respectively. Additionally, the increases during the COVID-19 period were greater than 91% of all historical 29-week periods analyzed.ConclusionsThe occurrence of EMS runs for opioid-related overdoses, naloxone administrations, and multiple naloxone administrations during EMS runs increased during the COVID-19 pandemic in Guilford County, NC. For a host of reasons that need to be explored, the COVID-19 pandemic appears to have exacerbated the opioid crisis. 相似文献
58.
59.
Muhammad Amjad Awan Javeria Arshad Bushra Allah Rakha Muhammad Sajjad Ansari Muhammad Waseem Ali Fouladi-Nashta David Miller Shamim Akhter 《Andrologia》2021,53(3):e13991
This study reports the first evaluation of sperm hyaluronan binding assay (HBA) for predicting the fertility of Nili-Ravi buffalo bulls in relation to standard parameters of sperm quality. Cryopreserved semen doses of low (n = 6), medium (n = 3) and high fertility (n = 8) bulls based on their respective return rates were used. Significantly, more spermatozoa bound to hyaluronan from the most fertile bulls (57.15% ± 1.44) compared with medium (42.46% ± 1.08) and low fertility bulls (29.70% ± 0.78). A strongly positive correlation (r = .824, p < .01) was found between HBA and fertility that predicts a 67.9% variability (r2 = .679, p < .01) in fertility. HBA was also strongly positively correlated with sperm viability (r = .679, p < .01) followed by their live/dead ratio (r = .637, p < .01), uncapacitated spermatozoa (r = .631, p < .01), normal apical ridge (r = .459, p < .01), motility (r = .434, p < .01), mature spermatozoa with low residual histones (r = .364, p < .01), high plasma membrane integrity (r = .316, p < .01) and nonfragmented DNA levels (r = .236, p < .05). It was negatively correlated with spermatozoa having reacted acrosome (r = −.654, p < .01). A fertility model built using a combination of sperm HBA and either sperm livability or viability predicts, respectively, 86.1% (r2 = .861, p < .01) and 85.9% (r2 = .859, p < .01) variability in buffalo bull fertility. In conclusion, sperm HBA may prove to be a single robust predictor of Nili-Ravi buffalo bull fertility. 相似文献
60.
Tutino Vincent M. Rajabzadeh-Oghaz Hamidreza Veeturi Sricharan S. Poppenberg Kerry E. Waqas Muhammad Mandelbaum Max Liaw Nicholas Siddiqui Adnan H. Meng Hui Kolega John 《Neurosurgical review》2021,44(5):2545-2570
Neurosurgical Review - The pathogenesis and natural history of intracranial aneurysm (IA) remains poorly understood. To this end, animal models with induced cerebral vessel lesions mimicking human... 相似文献