Comparison of thrombomodulin, vWF, and ADAMTS13 levels between preeclampsia and normal pregnancy

Objectives: To determine and compare plasma thrombomodulin, von Willebrand factor and von Willebrand factorcleaving protease levels between pre-eclamptic and healthy pregnant females. METHODS: The cross-sectional, comparative study was conducted at the Department of Haematology, University of Health Sciences, Lahore, Pakistan, from November 2019 to December 2020, and comprised pregnant females who were divided into healthy pregnant group A and pre-eclamptic group B. Plasma thrombomodulin and von Willebrand factor-cleaving protease levels were determined by using commercially available enzyme-linked immunosorbent assay kit, and von Willebrand factor level was determined by using immuno-turbidimetric assay kit. Data was analysed using SPSS 25. RESULTS: Of the 88 participants, there were 44(50%) females with mean age 25.5±6 years in group A and 44(50%) in group B with mean age 26±5 years. Median thrombomodulin level in group B was significantly higher than group A (p=0.003). Median von Willebrand factor-cleaving protease levels were lower in group B compared to group A (p=0.838). A significant difference in von Willebrand factor level was observed between the groups (p=0.038). Conclusion: Females with pre-eclampsia had significantly higher plasma levels of von Willebrand factor and thrombomodulin than healthy pregnant subjects.

The Hausa Northwick Park Neck Pain Questionnaire: translation, cross-cultural adaptation and psychometric assessment in patients with non-specific neck pain.

PURPOSE: To translate and cross-culturally adapt the Northwick Park Neck Pain Questionnaire (NPQ) into Hausa and assess its psychometric properties. MATERIALS AND METHODS: The NPQ was translated and cross-culturally adapted into Hausa using recommended guidelines. A consecutive sample of 92 Hausa-speaking patients with non-specific neck pain recruited from three tertiary hospitals in north-western Nigeria, completed the questionnaire to assess factorial validity (using confirmatory factor analysis), convergent validity (by correlating the Hausa-NPQ with the Numerical Pain Rating Scale [NPRS]), and internal consistency (using Cronbach's α). A subsample of 50 patients completed the questionnaire again 3 days after the first administration to assess relative reliability using intraclass correlation coefficients (ICC) and absolute reliability using standard error of measurement (SEM), smallest detectable change (SDC), and 95% limits of agreement (LOA). RESULTS: The factor analysis confirmed a single-factor structure with excellent internal consistency (α = 0.94). The questionnaire showed a strong positive correlation with the NPRS (rho = 0.68). The ICC was 0.86, with SEM and SDC of 6.32 and 17.5, respectively. The LOA was - 29.3 to + 37.1 with no evidence of proportional bias. CONCLUSIONS: The Hausa-NPQ is a valid and reliable measure of disability due to neck pain.

This study describes the translation, cross-cultural adaptation, and psychometric assessment of the Hausa-NPQ in Hausa-speaking patients with non-specific neck pain.The questionnaire demonstrated adequate psychometric properties in terms of factorial and convergent validity, internal consistency, and test-retest reliability.The questionnaire will be useful in clinical and research settings to assess disability due to neck pain for screening purposes, evaluation of treatment effectiveness, as well as cross-cultural comparisons involving Hausa-speaking individuals with neck pain.

Prevalence and correlates of undiagnosed hypertension among staff of a Nigerian university community.

Introduction: the prevalence of hypertension in Nigeria is high, with a considerable proportion of it being undiagnosed. Nevertheless, early identification of influencing variables for hypertension in different population groups is important for several reasons. This study aimed to determine the prevalence and correlates of undiagnosed hypertension among staff of a university community in Nigeria. Methods: a purposive sample of 281 staff of Bauchi State University, Gadau, Nigeria, fulfilled the inclusion criteria and were enrolled in this cross-sectional study. Demographics, blood pressure, height, weight, socioeconomic status and physical activity were measured. Diagnosis of hypertension was defined based on a systolic and diastolic blood pressure of ≥140 mmHg and ≥90 mmHg, respectively. Data obtained was analysed descriptively, and by means of Chi-square, univariate and multivariate statistics using SPSS v24 software. Results: the mean age and body mass index (BMI) of the participants was 34.5 years and 23.1 ± 5.17 Kg/m2, respectively. The prevalence rate of undiagnosed hypertension was 27.8%. Normotensives significantly differed from participants with undiagnosed hypertension in most of the clinical and demographic variables (p<0.05). Univariate and multivariate analyses revealed that a positive family history of hypertension had the highest odds of having undiagnosed hypertension (aOR: 0.833, 95%CI: 16.55-432.87, p= 0.000). Next, a higher BMI score (aOR: 0.425, 95%CI: 0.085-0.447, p= 0.000), male gender (aOR: 0.451, 95%CI: 0.141-0.829, p= 0.018), job cadre (aOR: 0.515, 95%CI: 0.073-0.550, p= 0.002) and low physical activity level (aOR: 0.572, 95%CI: 5.296-49.777, p=0.000) were other factors with about 50% odds for having undiagnosed hypertension among the participants. Lastly, smoking status and socioeconomic status of the participants were not significantly associated with undiagnosed hypertension (p>0.05). Conclusion: a high percentage of the studied population have undiagnosed hypertension that is mainly associated with non-modifiable (especially positive family history) and a few modifiable risk factors. These variables can be used for early identification and in designing appropriate preventive strategies.

CAMSAP3 facilitates basal body polarity and the formation of the central pair of microtubules in motile cilia.

Synchronized beating of cilia on multiciliated cells (MCCs) generates a directional flow of mucus across epithelia. This motility requires a "9 + 2" microtubule (MT) configuration in axonemes and the unidirectional array of basal bodies of cilia on the MCCs. However, it is not fully understood what components are needed for central MT-pair assembly as they are not continuous with basal bodies in contrast to the nine outer MT doublets. In this study, we discovered that a homozygous knockdown mouse model for MT minus-end regulator calmodulin-regulated spectrin-associated protein 3 (CAMSAP3), Camsap3tm1a/tm1a , exhibited multiple phenotypes, some of which are typical of primary ciliary dyskinesia (PCD), a condition caused by motile cilia defects. Anatomical examination of Camsap3tm1a/tm1a mice revealed severe nasal airway blockage and abnormal ciliary morphologies in nasal MCCs. MCCs from different tissues exhibited defective synchronized beating and ineffective generation of directional flow likely underlying the PCD-like phenotypes. In normal mice, CAMSAP3 localized to the base of axonemes and at the basal bodies in MCCs. However, in Camsap3tm1a/tm1a , MCCs lacked CAMSAP3 at the ciliary base. Importantly, the central MT pairs were missing in the majority of cilia, and the polarity of the basal bodies was disorganized. These phenotypes were further confirmed in MCCs of Xenopus embryos when CAMSAP3 expression was knocked down by morpholino injection. Taken together, we identified CAMSAP3 as being important for the formation of central MT pairs, proper orientation of basal bodies, and synchronized beating of motile cilia.

Health-related quality of life and related characteristics of persons with spinal cord injury in Nigeria.

Background: Spinal cord injury (SCI) is impairment of the spinal cord resulting in numerous health problems that considerably affect the quality of life (QOL) of the patients. Moreover, a number of sociodemographic and clinical characteristics may influence the persons' health-related quality of life (HRQOL). However, there is limited information on the HRQOL and related characteristics among affected persons living in Nigeria. This study explores the HRQOL and related characteristics of persons with SCI in Kano, Northwestern Nigeria. Methods: A prospective cross-sectional survey of 41 subjects with SCI and 40 age and gender matched healthy subjects was conducted from January to December 2016. Subjects' sociodemographic and clinical characteristics and HRQOL (using the SF-36 questionnaire) were collected and analyzed. Results: The majority of the subjects were men in both the SCI (85.4%) and healthy (82.5%) groups. The mean injury duration was 28.4 ± 20.2 months. Road traffic accident (46.3%) was the leading cause of injury with paraplegia (70.7%) being the most frequent level of injury. A greater number of the subjects (43.9%) had a complete impairment. Subjects with SCI had significantly lower HRQOL in the domains of general health, physical functioning, bodily pain, social functioning, role-emotional, and mental health compared to healthy controls. Gender, level of injury, and severity of injury were commonly found to be related to lower HRQOL scores. Conclusion: Persons with SCI from Kano, Northwestern Nigeria have lower HRQOL across various domains compared to healthy controls. Common factors related to lower HRQOL scores were gender, level of injury, and severity of injury. There is a need for optimal rehabilitation for persons with SCI in Kano, Northwestern Nigeria.

Codeficiency of Lysosomal Mucolipins 3 and 1 in Cochlear Hair Cells Diminishes Outer Hair Cell Longevity and Accelerates Age-Related Hearing Loss.

Acquired hearing loss is the predominant neurodegenerative condition associated with aging in humans. Although mutations on several genes are known to cause congenital deafness in newborns, few genes have been implicated in age-related hearing loss (ARHL), perhaps because its cause is likely polygenic. Here, we generated mice lacking lysosomal calcium channel mucolipins 3 and 1 and discovered that both male and female mice suffered a polygenic form of hearing loss. Whereas mucolipin 1 is ubiquitously expressed in all cells, mucolipin 3 is expressed in a small subset of cochlear cells, hair cells (HCs) and marginal cells of the stria vascularis, and very few other cell types. Mice lacking both mucolipins 3 and 1, but not either one alone, experienced hearing loss as early as at 1 month of age. The severity of hearing impairment progressed from high to low frequencies and increased with age. Early onset of ARHL in these mice was accompanied by outer HC (OHC) loss. Adult mice conditionally lacking mucolipins in HCs exhibited comparable auditory phenotypes, thereby revealing that the reason for OHC loss is mucolipin codeficiency in the HCs and not in the stria vascularis. Furthermore, we observed that OHCs lacking mucolipins contained abnormally enlarged lysosomes aggregated at the apical region of the cell, whereas other organelles appeared normal. We also demonstrated that these aberrant lysosomes in OHCs lost their membrane integrity through lysosomal membrane permeabilization, a known cause of cellular toxicity that explains why and how OHCs die, leading to premature ARHL.SIGNIFICANCE STATEMENT Presbycusis, or age-related hearing loss (ARHL), is a common characteristic of aging in mammals. Although many genes have been identified to cause deafness from birth in both humans and mice, only a few are known to associate with progressive ARHL, the most prevalent form of deafness. We have found that mice lacking two lysosomal channels, mucolipins 3 and 1, suffer accelerated ARHL due to auditory outer hair cell degeneration, the most common cause of hearing loss and neurodegenerative condition in humans. Lysosomes lacking mucolipins undergo organelle membrane permeabilization and promote cytotoxicity with age, revealing a novel mechanism of outer hair cell degeneration and ARHL. These results underscore the importance of lysosomes in hair cell survival and the maintenance of hearing.

Susceptibility of outer hair cells to cholesterol chelator 2-hydroxypropyl-ß-cyclodextrine is prestin-dependent.

Niemann-Pick type C1 disease (NPC1) is a fatal genetic disorder caused by impaired intracellular cholesterol trafficking. Recent studies reported ototoxicity of 2-hydroxypropyl- ß-cyclodextrin (HPßCD), a cholesterol chelator and the only promising treatment for NPC1. Because outer hair cells (OHCs) are the only cochlear cells affected by HPßCD, we investigated whether prestin, an OHC-specific motor protein, might be involved. Single, high-dose administration of HPßCD resulted in OHC death in prestin wildtype (WT) mice whereas OHCs were largely spared in prestin knockout (KO) mice in the basal region, implicating prestin's involvement in ototoxicity of HPßCD. We found that prestin can interact with cholesterol in vitro, suggesting that HPßCD-induced ototoxicity may involve disruption of this interaction. Time-lapse analysis revealed that OHCs isolated from WT animals rapidly deteriorated upon HPßCD treatment while those from prestin-KOs tolerated the same regimen. These results suggest that a prestin-dependent mechanism contributes to HPßCD ototoxicity.

Increased Spontaneous Otoacoustic Emissions in Mice with a Detached Tectorial Membrane.

Mutations in genes encoding tectorial membrane (TM) proteins are a significant cause of human hereditary hearing loss (Hildebrand et al. 2011), and several mouse models have been developed to study the functional significance of this accessory structure in the mammalian cochlea. In this study, we use otoacoustic emissions (OAE), signals obtained from the ear canal that provide a measure of cochlear function, to characterize a mouse in which the TM is detached from the spiral limbus due to an absence of otoancorin (Otoa, Lukashkin et al. 2012). Our results demonstrate that spontaneous emissions (SOAE), sounds produced in the cochlea without stimulation, increase dramatically in mice with detached TMs even though their hearing sensitivity is reduced. This behavior is unusual because wild-type (WT) controls are rarely spontaneous emitters. SOAEs in mice lacking Otoa predominate around 7 kHz, which is much lower than in either WT animals when they generate SOAEs or in mutant mice in which the TM protein Ceacam16 is absent (Cheatham et al. 2014). Although both mutants lack Hensen's stripe, loss of this TM feature is only observed in regions coding frequencies greater than ~15 kHz in WT mice so its loss cannot explain the low-frequency, de novo SOAEs observed in mice lacking Otoa. The fact that ~80 % of mice lacking Otoa produce SOAEs even when they generate smaller distortion product OAEs suggests that the active process is still functioning in these mutants but the system(s) involved have become less stable due to alterations in TM structure.