Manipulation and mobilization for treating chronic low back pain: a systematic review and meta-analysis

Mobilization and manipulation therapies are widely used to benefit patients with chronic low back pain. However, questions remain about their efficacy, dosing, safety, as well as how these approaches compare to other therapies.

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Complex signatures of natural selection at GYPA

Abstract

The human MN blood group antigens are isoforms of glycophorin A (GPA) encoded by the gene, GYPA, and are the most abundant erythrocyte sialoglycoproteins. The distribution of MN antigens has been widely studied in human populations yet the evolutionary and/or demographic factors affecting population variation remain elusive. While the primary function of GPA is yet to be discovered, it serves as the major binding site for the 175-kD erythrocyte-binding antigen (EB-175) of the malarial parasite, Plasmodium falciparum, a major selective pressure in recent human history. More specifically, exon two of GYPA encodes the receptor-binding ligand to which P. falciparum binds. Accordingly, there has been keen interest in understanding what impact, if any, natural selection has had on the distribution of variation in GYPA and exon two in particular. To this end, we resequenced GYPA in individuals sampled from both P. falciparum endemic (sub-Saharan Africa and South India) and non-endemic (Europe and East Asia) regions of the world. Observed patterns of variation suggest that GYPA has been subject to balancing selection in populations living in malaria endemic areas and in Europeans, but no such evidence was found in samples from East Asia, Oceania, and the Americas. These results are consistent with malaria acting as a selective pressure on GYPA, but also suggest that another selective force has resulted in a similar pattern of variation in Europeans. Accordingly, GYPA has perhaps a more complex evolutionary history, wherein on a global scale, spatially varying selective pressures have governed its natural history.

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The role of hypoxia-inducible factors in carotid body (patho) physiology

Abstract

Hypoxia-inducible factors mediate adaptive responses to reduced O₂ availability. In patients with obstructive sleep apnea, repeated episodes of hypoxemia and reoxygenation (intermittent hypoxia) are sensed by the carotid body (CB). The ensuing CB chemosensory reflex activates the sympathetic nervous system and increased secretion of catecholamines by the adrenal medulla, resulting in hypertension and breathing abnormalities. In the CB, intermittent hypoxia induces the formation of reactive oxygen species (ROS) and increased intracellular Ca²⁺ levels, which drive increased expression of hypoxia-inducible factor 1α (HIF-1α) and a decrease in the levels of HIF-2α.  Intermittent hypoxia increases HIF-1α-dependent expression of Nox2, encoding the pro-oxidant enzyme NADPH oxidase 2, and decreased HIF-2α-dependent expression of Sod2, encoding the anti-oxidant enzyme superoxide dismutase 2. These changes in gene expression drive persistently elevated ROS levels in the CB, brainstem, and adrenal medulla that are required for the development of hypertension and breathing abnormalities. The ROS generated by dysregulated HIF activity in the CB results in oxidation and inhibition of heme oxygenase 2, and the resulting reduction in the levels of carbon monoxide lead to increased hydrogen sulfide production, triggering glomus cell depolarization. Thus, the pathophysiology of obstructive sleep apnea involves the dysregulation of O₂-regulated transcription factors, gasotransmitters, and sympathetic outflow that affects blood pressure and breathing.

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Sympatholysis: the more we learn, the less we know

Abstract

During exercise, blood is redistributed to meet the metabolic demands of the working skeletal muscle and to regulate core temperature and systemic haemodynamics, primarily mean arterial pressure.

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Benign and malignant tumors in Rubinstein–Taybi syndrome

Rubinstein–Taybi syndrome (RSTS) is a multiple congenital anomalies syndrome associated with mutations in CREBBP (70%) and EP300 (5–10%). Previous reports have suggested an increased incidence of specific benign and possibly also malignant tumors. We identified all known individuals diagnosed with RSTS in the Netherlands until 2015 (n = 87) and studied the incidence and character of neoplastic tumors in relation to their CREBBP/EP300 alterations. The population–based Dutch RSTS data are compared to similar data of the Dutch general population and to an overview of case reports and series of all RSTS individuals with tumors reported in the literature to date. Using the Nationwide Network and Registry of Histopathology and Cytopathology in the Netherlands (PALGA Foundation), 35 benign and malignant tumors were observed in 26/87 individuals. Meningiomas and pilomatricomas were the most frequent benign tumors and their incidence was significantly elevated in comparison to the general Dutch population. Five malignant tumors were observed in four persons with RSTS (medulloblastoma; diffuse large-cell B-cell lymphoma; breast cancer; non-small cell lung carcinoma; colon carcinoma). No clear genotype–phenotype correlation became evident. The Dutch population-based data and reported case studies underscore the increased incidence of meningiomas and pilomatricomas in individuals with RSTS. There is no supporting evidence for an increased risk for malignant tumors in individuals with RSTS, however, due to the small numbers this risk may not be fully dismissed.

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Clinical features, BTD gene mutations, and their functional studies of eight symptomatic patients with biotinidase deficiency from Southern China

Biotinidase (BTD) deficiency is a rare autosomal recessive metabolic disease, which develops neurological and cutaneous symptoms because of the impaired biotin recycling. Pathogenic mutations on BTD gene cause BTD deficiency. Clinical features and mutation analysis of Chinese children with BTD deficiency were rarely described. Herein, for the first time, we reported the clinical features, BTD gene mutations and their functional studies of eight symptomatic children with BTD deficiency from southern China. Fatigue, hypotonia, proximal muscular weakness, hearing deficits, rash and respiratory problems are common clinical phenotype of our patients. Seizures are observed only in patients with profound BTD deficiency. Five novel mutations were detected, among which c.637delC (H213TfsTer51) was found in 50% of our patients and might be considered as a common mutation. In vitro studies confirmed three mild mutations c.1368A>C (Q456H), c.1613G>A (R538H), and c.644T>A (L215H) which retained 10–30% of wild type enzyme activity, and six severe mutations c.235C>T (R79C), c.1271G>C (C424S), c.1412G>A (C471Y), c.637delC (H213TfsTer51), c.395T>G (M132W), c.464T>C (L155P), and c.1493dupT (L498FfsTer13) which retained <10% of wild type enzyme activity. c.1330G>C (D444H) decreased the protein expression but not activity of BTD enzyme, and H213TfsTer51 was structurally damaging while L498FfsTer13 was functionally damaging. These results will be helpful in establishing the definitive diagnosis of BTD deficiency at the gene level, offering appropriate genetic counseling, and providing clues to structure/function relationships of the enzyme.

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Ultrasound-guided lumbar plexus block in children and adolescents using a transverse lumbar paravertebral sonogram: Initial experience

Summary

Background

The clinical reliability and reproducibility of ultrasound-guided lumbar plexus blocks is not established in pediatric populations. We present the results of a combined nerve stimulation ultrasound-guided lumbar plexus block using the vertebral body, transverse process, and psoas muscle as landmarks on a transverse lumbar paravertebral sonogram with mid-axillary transducer placement, "shamrock method," in children and adolescents.

Aims

Our primary objective was to determine the rate of achieving sensory changes in the lumbar plexus distribution. Secondary outcomes were performance time, reliability of echo-landmarks, measures of patient comfort, and complications.

Methods

We reviewed prospectively collected quality assurance data and electronic medical records of 21 patients having major orthopedic surgery with lumbar plexus block catheter for postoperative analgesia.

Results

Twenty-one patients were studied with mean age and weight (SD, range) of 13.6 years (3.8, 6-18) and 49.3 kg (18.6, 19.2-87.6). Surgical procedures included periacetabular osteotomy, pelvic osteotomy, and proximal femoral osteotomy. Mean volume of 0.5 mL/kg (0.05) 0.2% ropivacaine produced thermal sensory changes to femoral and lateral femoral cutaneous nerves in 20/21 (95% CI 0.76 to >0.99) and 19/21 (95% CI 0.70-0.99) patients. Identification of transverse process (TP), vertebral body (VB), and psoas muscle (PM): 21/21 (95% CI 0.86-1.0). Average block performance time was 9:08 minutes (2:09, 2-13). Average opioid consumption (SD) in operating room, postanesthesia care unit, 0-12 and 12-24-hour periods were 0.17 mg/kg (0.08), 0.08 mg/kg (0.06), 0.06 mg/kg (0.06), and 0.06 mg/kg (0.05). Median pain score by severity category in postanesthesia care unit: (0-3) 66.7%, (4-6) 28.5%, (>7) 4.8%; 0-12 hours: (0-3) 76.2%, (4-6) 19.0%, (>7) 4.8%; 12-24 hours: (0-3) 57.2%, (4-6) 42.8%, (>7) 0%. No complications were recorded.

Conclusion

Ultrasound guidance using lateral imaging of transverse process, vertebral body, and psoas muscle allows practitioners to reach the nerves of the lumbar plexus and achieve sensory block in pediatric patients with a high success rate.

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