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1.
Microcephaly is a frequent feature of neurodevelopmental disorders (NDDs). Our study presents the heterogeneous spectrum of genetic disorders in patients with microcephaly either in isolated form or in association with other neurological and extra-neural abnormalities. We present data of 91 patients from 87 unrelated families referred to our clinic during 2016–2020 and provide a comprehensive clinical and genetic landscape in the studied cohort. Molecular diagnosis using exome sequencing was made in 45 families giving a yield of 51.7%. In 9 additional families probable causative variants were detected. We identified disease causing variations in 49 genes that are involved in different functional pathways Among these, 36 had an autosomal recessive pattern, 8 had an autosomal dominant pattern (all inherited de novo), and 5 had an X-linked pattern. In 41 probands where sequence variations in autosomal recessive genes were identified 31 were homozygotes (including 16 from non-consanguineous families). The study added 28 novel pathogenic/likely pathogenic variations. The study also calls attention to phenotypic variability and expansion in spectrum as well as uncovers genes where microcephaly is not reported previously or is a rare finding. We here report phenotypes associated with the genes for ultra-rare NDDs with microcephaly namely ATRIP, MINPP1, PNPLA8, AIMP2, ANKLE2, NCAPD2 and TRIT1.  相似文献   
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Wnt signaling plays key roles in many aspects of development. In this review, we will briefly describe the components of signaling pathways induced by Wnt ligands and then describe the current state of research as this applies to aspects of development and disease as it relates to skeletal muscle and bone. We will conclude with a discussion of the parallels and differences in Wnt signaling in these two contexts and how these pathways are being (or could potentially be) targeted for therapeutic treatment of musculoskeletal diseases.This article is part of a Special Issue entitled “Muscle Bone Interactions”.  相似文献   
4.
《Injury》2022,53(2):676-682
Aim3D-printed implants could improve the capture of fracture fragments for improved stability of tibial plateau fracture fixation. The aim of this study was to compare the biomechanical strength of fixation constructs using standard and customised 3D-printed proximal tibial locking plates for fixation of tibial plateau fractures.MethodsThis is a biomechanical study utilising six pairs of cadaveric tibiae. Fractures were created in an identical fashion using an osteotome and mallet, and fixed using either a standard, commercially-available proximal tibia locking plate or a customised 3D-printed plate. Design and production of the customised plates followed a “3D printing at point-of-care” model. Customised stainless steel 316 L plates were produced within a local additive manufacturing laboratory based upon pre-operative CT scans. Determination of implant choice within each cadaver pair was performed via simple randomisation. Following fracture fixation, the tibiae were skeletalised and biomechanically tested using a customised loading jig and a size-matched femoral knee prosthesis. The constructs were loaded cyclically from 100 N to approximately three times the cadaveric body-weight at 5 Hz for 10 000 cycles. Every 1000 cycles, the test was paused and the tibia was physically checked for failure. If failure had not occurred by the end of the testing cycle, the construct was loaded to failure and the load at which the construct failed was noted.ResultsFixation constructs using the 3D-printed plates performed comparably to those using the standard plates. There was no significant difference in the degree of fracture fragment displacement in both constructs. Overall longitudinal construct stiffness and load to failure was higher in the 3D-plates group but this did not reach statistical significance.ConclusionProduction of customised plates for proximal tibia fractures at point-of-care is feasible, however fixation constructs with these plates did not provide any biomechanical advantage over standard plates in terms of axial loading stiffness.  相似文献   
5.
Arthroscopic acromioclavicular joint excision is a commonly performed but technically demanding procedure. Incomplete excision can leave residual symptoms. We present a simple, reproducible technique ensuring satisfactory excision of the joint.  相似文献   
6.
BackgroundDyslipidemia in rheumatoid arthritis (RA) patients is frequently observed, and treatment with anti-rheumatic drugs has an impact on lipid profiles. Pathophysiologically, inflammation leads to decreased blood lipids and lipoproteins; RA treatment reduces inflammation and therefore may increase lipids and lipoproteins. Whether the lipid changes with RA treatment confer an increased risk of cardiovascular disease or just reflect their potentially atheroprotective anti-inflammatory effect is currently unclear due to limited and conflicting data.ObjectiveThe aim of this review is to summarize the current knowledge on the effects of synthetic and biological disease modifying antirheumatic drugs for the treatment of RA on lipid and lipoprotein parameters.ResultsRecent studies on methotrexate emphasize its anti-atherogenic effect. Golimumab combined with methotrexate revealed a trend towards an anti-atherogenic potential. The known pro-atherogenic lipid-spectrum alterations caused by tofacitinib can be effectively treated with atorvastatin. Tocilizumab signals a favorable impact on the extent of lipid modifications when combined with methotrexate. Abatacept indicated a trend towards an anti-atherogenic lipid profile demonstrated by favorable effects on HDL-C and on the TC/HDL-C ratio. Rituximab has beneficial effects on HDL-C and ApoA1, as well as on the ApoB/ApoA1 ratio.Clinical implicationsAnti-rheumatic drugs have various effects on lipid parameters, which in part appear pro-atherogenic. However, because many of these lipid changes may well reflect their potentially atheroprotective anti-inflammatory action the cardiovascular impact of these changes remains unclear. Whatsoever, cardiovascular safety trials for antirheumatic drugs would be valuable.  相似文献   
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Osteoporosis and sarcopenia are common in older age and associated with significant morbidity and mortality. Consequently, they are both attended by a considerable socioeconomic burden. Osteoporosis was defined by the World Health Organisation (WHO) in 1994 as a bone mineral density of less than 2.5 standard deviations below the sex-specific young adult mean and this characterisation has been adopted globally. Subsequently, a further step forward was taken when bone mineral density was incorporated into fracture risk prediction algorithms, such as the Fracture Risk Assessment Tool (FRAX®) also developed by the WHO. In contrast, for sarcopenia there have been several diagnostic criteria suggested, initially relating to low muscle mass alone and more recently low muscle mass and muscle function. However, none of these have been universally accepted. This has led to difficulties in accurately delineating the burden of disease, exploring geographic differences, and recruiting appropriate subjects to clinical trials. There is also uncertainty about how improvement in sarcopenia should be measured in pharmaceutical trials. Reasons for these difficulties include the number of facets of muscle health available, e.g. mass, strength, function, and performance, and the various clinical outcomes to which sarcopenia can be related such as falls, fracture, disability and premature mortality. It is imperative that a universal definition of sarcopenia is reached soon to facilitate greater progress in research into this debilitating condition.This article is part of a Special Issue entitled “Muscle Bone Interactions”.  相似文献   
9.
ABSTRACT

Objective

To investigate primary care physician clinical practice patterns, barriers, and education surrounding pediatric physical activity (PA), and to compare practice patterns by discipline.  相似文献   
10.

Background Context

Low back pain (LBP) is a common complaint in clinical practice of multifactorial origin. Although obesity has been thought to contribute to LBP primarily by altering the distribution of mechanical loads on the spine, the additional contribution of obesity-related conditions such as diabetes mellitus (DM) to LBP has not been thoroughly examined.

Purpose

To determine if there is a relationship between DM and LBP that is independent of body mass index (BMI) in a large cohort of adult survey participants.

Study Design

Retrospective analysis of prospectively collected National Health and Nutrition Examination Survey (NHANES) data to characterize associations between LBP, DM, and BMI in adults subdivided into 6 subpopulations: normal weight (BMI 18.5–25), overweight (BMI 25–30), and obese (BMI >30) diabetics and nondiabetics. Diabetes was defined with glycohemoglobin A1c (HbA1c) 6.5%.

Patient Sample

11,756 participants from NHANES cohort.

Outcome Measures

Percentage of LBP reported.

Methods

LBP reported in the 1999-2004 miscellaneous pain NHANES questionnaire was the dependent variable examined. Covariates included HbA1c, BMI, age, and family income ratio to poverty as continuous variables as well as race, gender, and smoking as binary variables. Individuals were further subdivided by weight class and diabetes status. Regression and graphical analyses were performed on the study population as a whole and also on subpopulations.

Results

Increasing HbA1c did not increase the odds of reporting LBP in the full cohort. However, multivariate logistic regression of the 6 subpopulations revealed that the odds of LBP significantly increased with increasing HbA1c levels in normal weight diabetics. No other subpopulations reported significant relationships between LBP and HbA1c. LBP was also significantly associated with BMI for normal weight diabetics and also for obese subjects regardless of their DM status.

Conclusions

LBP is significantly related to DM status, but this relationship is complex and may interact with BMI. These results support the concept that LBP may be improved in normal weight diabetic subjects with improved glycemic control and weight loss, and that all obese LBP subjects may benefit from improved weight loss alone.  相似文献   
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