Tag: nevin manimala

J Inherit Metab Dis. 2021 Aug 21. doi: 10.1002/jimd.12428. Online ahead of print.

ABSTRACT

BACKGROUND: Niemann-Pick disease type C (NPC) is a rare, genetic, progressive neurodegenerative disorder with high unmet medical need. We investigated the safety and efficacy of arimoclomol, which amplifies the heat shock response to target NPC protein misfolding and improve lysosomal function, in patients with NPC.

METHODS: In a 12-month, prospective, randomized, double-blind, placebo-controlled, phase 2/3 trial (ClinicalTrials.gov identifier: NCT02612129), patients (2-18 years) were randomized 2:1 to arimoclomol:placebo, stratified by miglustat use. Routine clinical care was maintained. Arimoclomol was administered orally three times daily. The primary endpoint was change in 5-domain NPC Clinical Severity Scale (NPCCSS) score from baseline to 12 months.

RESULTS: Fifty patients enrolled; 42 completed. At month 12, the mean progression from baseline in the 5-domain NPCCSS was 0.76 with arimoclomol versus 2.15 with placebo. A statistically significant treatment difference in favour of arimoclomol of -1.40 (95% confidence interval: -2.76, -0.03; p = 0.046) was observed, corresponding to a 65% reduction in annual disease progression. In the prespecified subgroup of patients receiving miglustat as routine care, arimoclomol resulted in stabilization of disease severity over 12 months with a treatment difference of -2.06 in favour of arimoclomol (p = 0.006). Adverse events occurred in 30/34 patients (88.2%) receiving arimoclomol and 12/16 (75.0%) receiving placebo. Fewer patients had serious adverse events with arimoclomol (5/34, 14.7%) versus placebo (5/16, 31.3%). Treatment-related serious adverse events (n = 2) included urticaria and angioedema.

CONCLUSIONS: Arimoclomol provided a significant and clinically meaningful treatment effect in NPC and was well tolerated. This article is protected by copyright. All rights reserved.

PMID:34418116 | DOI:10.1002/jimd.12428

Equine Vet J. 2021 Aug 21. doi: 10.1111/evj.13498. Online ahead of print.

ABSTRACT

BACKGROUND: Incisional complications are a common cause of morbidity following laparotomy. Although uncommon, acute abdominal dehiscence (AAD) is a potentially fatal post-operative complication. However few AAD cases are described in the literature.

OBJECTIVES: To describe common features of cases of AAD following ventral midline laparotomy, management and outcomes.

STUDY DESIGN: Retrospective case series.

METHODS: Hospital records of horses that underwent a ventral midline laparotomy at nine hospitals in the UK, Ireland and USA over a 10-year period (2009-2019) were reviewed. Data were collected for pre-, intra- and post-operative factors that were considered relevant. Descriptive statistical analysis was performed.

RESULTS: A total of 63 cases of AAD were identified. AAD occurred due to tearing of sutures through the linea alba or rupture of the body wall adjacent to the suture line in 46 horses (73%). AAD occurred at a median of 5 days (0.5-70 days) post-operatively and broodmares accounted for 25% of the cases (n=16). Surgical site infection developed prior to AAD in 28 horses (44%); leakage of peritoneal fluid occurred in 5% of horses prior to AAD being identified. Surgical repair was performed in 27 horses (43%), 10 (16%) were treated conservatively and 26 (41%) were euthanased immediately. Repair was most frequently performed using suture (n=14), wire (n=5) or a combination (n=5). Overall survival to hospital discharge was 39% (24/63). Where surgical repair was performed, 15 horses (56%) survived to hospital discharge; 9 horses (90%) managed conservatively survived to hospital discharge.

MAIN LIMITATIONS: Follow-up was not performed for all cases following hospital discharge and some data were incompletely recorded in hospital files.

CONCLUSIONS: Previously stated causative factors for AAD were not consistent features in the present study. Surgical site infection following laparotomy and pregnant or early post-partum mares may be important risk factors for AAD and warrant further investigation.

PMID:34418125 | DOI:10.1111/evj.13498

J Ultrasound Med. 2021 Aug 21. doi: 10.1002/jum.15814. Online ahead of print.

ABSTRACT

OBJECTIVES: Intussusception is one of the most common abdominal emergencies in early children. Intussusception recurs in 8-20% of children after successful nonoperative reduction. The aim of this study was to explore the ultrasound findings to predict risk of recurrence in pediatric intussusception after air enema reduction.

METHODS: A total of 336 intussusception children were followed up for 1 year after received successful air enema reduction. They were divided into the recurrent group and the non-recurrent group. The differences of clinical characteristics, ultrasonic features, and laboratory tests were analyzed by univariate analyses and the Cox proportional hazard model.

RESULTS: Sixty-five children with recurrent intussusception were identified. There were statistically significances in the diameter of the mass, in the presence or absence of enlarged lymph nodes out of the sleeve, and in the sleeve between recurrent and non-recurrent groups (P < .05). Other ultrasonic features, clinical characteristics, and blood parameters had no differences (P > .05). Multivariate Cox proportional hazard model showed that the diameter of the mass and abdominal lymph nodes may be the risk factors of intussusception recurrence (HR = 1.395, 95% CI: 1.045~1.863 and HR = 2.078, 95% CI: 1.118~3.865, P < .05). The cut-off value of mass diameter was 2.55 cm, above which recurrence is more likely.

CONCLUSIONS: Intussusception recurrence was prone with greater mass diameter (>2.55 cm) and enlarged abdominal lymph nodes. Although these ultrasound findings for recurrence do not necessarily reduce the rate of recurrence, it can predict the recurrent possibility, and help the emergency physicians to be more vigilant in these children and better counsel parents upon discharge.

PMID:34418137 | DOI:10.1002/jum.15814

Int J Gynaecol Obstet. 2021 Aug 21. doi: 10.1002/ijgo.13895. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the role of hydrosalpinx in the susceptibility of chronic endometritis (CE).

METHODS: This is a retrospective cohort study, which includes 624 patients with hydrosalpinx (group A) and 789 patients without hydrosalpinx (group B) undergoing laparoscopy and hysteroscopy simultaneously. Endometrial morphology was recorded under hysteroscopy. Endometrial biopsy was obtained after hysteroscopy, and immunohistochemical staining for syndecan-1 (CD138) was carried out.

RESULTS: No significantly statistical differences were found between the two groups when comparing the incidence of endometrial hyperemia or endometrial micro-polyps under hysteroscopy (P>0.05). Hydrosalpinx had a significant impact on the incidence of CE (P<0.05) (plasma cell count: no plasma cells: OR 0.71, 95% CI 0.58-0.88, P=0.002; ≥1/HPF: OR 1.40, 95% CI 1.14-1.74, P=0.002; ≥3/HPF: OR 1.50, 95% CI 1.18-1.91, P=0.001; ≥5/HPF: OR 1.62, 95% CI 1.27-2.21, P<0.001). There were no significant differences in the comparison of plasma cell count between the unilateral hydrosalpinx group (274 patients) and the bilateral hydrosalpinx group (350 patients) (P>0.05).

CONCLUSION: The presence of hydrosalpinx increased the incidence of CE. Bilateral hydrosalpinx did not significantly increase the incidence of CE compared with unilateral hydrosalpinx.

PMID:34418100 | DOI:10.1002/ijgo.13895

Med Phys. 2021 Aug 21. doi: 10.1002/mp.15174. Online ahead of print.

ABSTRACT

PURPOSE: The substitution of Computerized Tomography with Magnetic Resonance Imaging has been investigated for external radiotherapy treatment planning. The present study aims to use Pseudo-CT images created by MRI images to calculate the dose distribution for facilitating in the treatment planning process.

METHODS: In this work, following image segmentation with a fuzzy clustering algorithm, an adaptive neuro-fuzzy algorithm was utilized to design the Hounsfield Unit conversion model based on the features vector of MRI images. The model was generated on the set of extracted features from gray level co-occurrence matrices, and the gray level run length matrices for 14 arbitrarily selected patients with brain malady. The performance of the algorithm was investigated on a blind datasets through dose-volume histogram and isodose curve evaluations, using the RayPlan treatment planning system, along with the gamma analysis and statistical indices.

RESULTS: In the proposed approach the mean absolute error within the range of 45.4 HU (Hounsfield unit) was found among the test data. Also, the relative dose difference between the planning target volume region of the CT and the Pseudo-CT was 0.5%, and the best gamma pass rate for 3%/3mm was 97.2%.

CONCLUSION: The proposed method provides a satisfactory average error rate for the generation of Pseudo-CT data in the different parts of the brain region from a collection of MRI series. Also, dosimetric parameters evaluation shows good agreement between reference CT and related Pseudo-CT images. This article is protected by copyright. All rights reserved.

PMID:34418104 | DOI:10.1002/mp.15174

Am J Phys Anthropol. 2021 Aug 21. doi: 10.1002/ajpa.24394. Online ahead of print.

ABSTRACT

OBJECTIVE: Frailty is the physiological stress that individuals suffer during their life. In past populations, frailty is conventionally assessed through the occurrence of different biomarkers of biological stress. Some efforts have been made to propose indexes that combine all biomarkers. However, these indices have some critical limitations: they cannot be used on incomplete skeletons, do not consider the severity and/or healing of lesions, and assign equal importance to different biomarkers. To address these limitations, we propose a new index to assess frailty in skeletal individuals.

MATERIAL AND METHODS: By statistically analyzing a large amount of osteological data available from the Museum of London, and using a Logit model, we were able to define a different weight for each reported biomarker of frailty, based on their importance in increasing the risk of premature death for the individuals.

RESULTS: The biological index of frailty (BIF) is the weighted mean of all biomarkers scored on the individuals, according to a different degree of importance assigned to each one. It also considers the severity and healing of the biomarkers when this is relevant to diagnose frailty. We applied BIF on a sample of Monastics and Non-Monastics from medieval England and compared it with the skeletal index of frailty (SFI).

DISCUSSION: BIF is the first frailty index that gives a different weight to each skeletal biomarker of stress, considers both severity and healing of the lesions, and can be applied on partial skeletal remains. The comparison with SFI showed that BIF is applicable to a larger number of skeletal individuals, revealing new differences between the Monastic and the Non-Monastic groups.

PMID:34418072 | DOI:10.1002/ajpa.24394

J Physiol. 2021 Aug 21. doi: 10.1113/JP281901. Online ahead of print.

ABSTRACT

Sensory stimulation of forelimb produces cortical evoked responses in the somatosensory hindlimb cortex in a layer-dependent manner Spinal cord injury favours the input statistics of cortico-cortical connections between intact and deafferented cortices After spinal cord injury supragranular layers exhibit better integration of spontaneous of corticocortical information while infragranular layers exhibit better integration of evoked sensory stimulation Cortical reorganization is a layer-specific phenomenon ABSTRACT: Cortical areas have the capacity of large-scale reorganization following sensory deafferentation. However, it remains unclear whether this phenomenon is a unique process that homogenously affects an entire deprived cortical region or it is suitable to changes depending on neuronal networks across distinct cortical layers. Here, we studied how local circuitries within each layer of the deafferented cortex set the basis for neuroplastic changes after immediate thoracic spinal cord injury (SCI) in anaesthetised rats. In vivo electrophysiological recordings from deafferented hindlimb somatosensory cortex showed that SCI induces layer-specific changes mediating evoked and spontaneous activity. In supragranular layers 2/3, SCI increased gamma oscillations and the ability of these neurons to initiate up-states during spontaneous activity, suggesting altered corticocortical network and/or intrinsic properties that may serve to maintain the excitability of the cortical column after deafferentation. On the other hand, SCI enhanced infragranular layers’ ability to integrate evoked-sensory inputs leading to increased and faster neuronal responses. Delayed evoked-responses onset were also observed in layers 5/6, suggesting alterations in thalamocortical connectivity. Altogether, our data indicate that SCI immediately modifies local circuitries within the deafferented cortex allowing supragranular layers to better integrate spontaneous corticocortical information, and thus modifying column excitability, and infragranular layers to better integrate evoked-sensory inputs to preserve subcortical outputs. These layer-specific neuronal changes may guide the long-term alterations in neuronal excitability and plasticity associated to the rearrangements of somatosensory networks and the appearance of central sensory pathologies usually associated with spinal cord injury. This article is protected by copyright. All rights reserved.

PMID:34418097 | DOI:10.1113/JP281901

J Pak Med Assoc. 2021 Aug;71(8):2065-2068. doi: 10.47391/JPMA.954.

ABSTRACT

The study investigates the determinants of the nutritional status of mothers in developing countries. For a panel of 38 developing countries, data were obtained from the nationally representative Demographic and Health Surveys (DHS). Married women of reproductive age group (15 to 45 years), currently living with their husbands were selected as the target population. Body mass index was used as a proxy measure to gauge the nutritional status. Both bivariate and multivariate statistical analyses were employed to assess the socioeconomic determinants of mothers’ nutritional status. The findings from both descriptive and probability analyses identified the mothers’ poor educational status, early marriage, high fertility rate, low birth interval, low women empowerment status, household poverty, and belonging to rural areas as the main determinants of poor nutritional status of mothers in developing countries; hence, there is a need to focus more on this group in order to stop the sustained transmission of intergenerational malnutrition.

PMID:34418031 | DOI:10.47391/JPMA.954

Biostatistics. 2021 Aug 21:kxab031. doi: 10.1093/biostatistics/kxab031. Online ahead of print.

ABSTRACT

Despite interest in the joint modeling of multiple functional responses such as diffusion properties in neuroimaging, robust statistical methods appropriate for this task are lacking. To address this need, we propose a varying coefficient quantile regression model able to handle bivariate functional responses. Our work supports innovative insights into biomedical data by modeling the joint distribution of functional variables over their domains and across clinical covariates. We propose an estimation procedure based on the alternating direction method of multipliers and propagation separation algorithms to estimate varying coefficients using a B-spline basis and an $L_2$ smoothness penalty that encourages interpretability. A simulation study and an application to a real-world neurodevelopmental data set demonstrates the performance of our model and the insights provided by modeling functional fractional anisotropy and mean diffusivity jointly and their association with gestational age and sex.

PMID:34418057 | DOI:10.1093/biostatistics/kxab031

Adv Ther. 2021 Aug 21. doi: 10.1007/s12325-021-01861-0. Online ahead of print.

ABSTRACT

Symptoms of anxiety and depression often coexist, and evidence suggests that this has a genetic basis, among other possible causes. However, the current classification of comorbid generalised anxiety disorder (GAD) and depression (anxious depression) in the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition; DSM-5) does not fully reflect the high prevalence of anxiety symptoms in people with depression and the International Classification of Diseases (10th and 11th revisions) has tended to identify anxious depression with minor disorders seen in primary care. As a result, few dedicated therapeutic trials have been conducted in patients with anxious depression, and specific treatment guidelines and recommendations are lacking. Fortunately, there is considerable therapeutic overlap between anxiety and depression, such that many agents with antidepressant efficacy are also effective for symptoms of GAD. The initial treatment of a patient with depression and symptoms of anxiety should be with an agent that is approved for both major depressive disorder and GAD, such as a selective serotonin reuptake inhibitor. There is an obvious need for greater recognition of anxious depression in order to boost the volume of high-quality clinical data, which should translate over time into better, more specific treatment recommendations and improved outcomes.

PMID:34417993 | DOI:10.1007/s12325-021-01861-0