Osteoporosis in ankylosing spondylitis

Ankylosing spondylitis (AS) is a chronic inflammatory disorder, characterized by an inflammatory enthesopathy progressing to ossification and ankylosis. Osteoporosis is a well‐reported complication of AS. Bone loss begins early in the disease at the spine, and later progresses to the hip. This reduction in bone density leads to an increased risk of fractures. However, there is a lack of awareness regarding this common complication, thus adding to the morbidity associated with AS. Early recognition, appropriate assessment and timely treatment of this complication will help reduce the attendant fracture risk due to decreased bone mass.     

Measuring Global Surgical Disparities: A Survey of Surgical and Anesthesia Infrastructure in Bangladesh

Background

Surgically treatable diseases weigh heavily on the lives of people in resource-poor countries. Though global surgical disparities are increasingly recognized as a public health priority, the extent of these disparities is unknown because of a lack of data. The present study sought to measure surgical and anesthesia infrastructure in Bangladesh as part of an international study assessing surgical and anesthesia capacity in low income nations.

Methods

A comprehensive survey tool was administered via convenience sampling at one public district hospital and one public tertiary care hospital in each of the seven administrative divisions of Bangladesh.

Results

There are an estimated 1,200 obstetricians, 2,615 general and subspecialist surgeons, and 850 anesthesiologists in Bangladesh. These numbers correspond to 0.24 surgical providers per 10,000 people and 0.05 anesthesiologists per 10,000 people. Surveyed hospitals performed a large number of operations annually despite having minimal clinical human resources and inadequate physical infrastructure. Shortages in equipment and/or essential medicines were reported at all hospitals and these shortages were particularly severe at the district hospital level.

Conclusions

In order to meet the immense demand for surgical care in Bangladesh, public hospitals must address critical shortages in skilled human resources, inadequate physical infrastructure, and low availability of equipment and essential medications. This study identified numerous areas in which the international community can play a vital role in increasing surgical and anesthesia capacity in Bangladesh and ensuring safe surgery for all in the country.     

Pregnancy related symptomatic vertebral hemangioma

Vertebral hemangiomas are benign vascular tumors of the spine that remain asymptomatic in most cases and incidentally encountered on imaging. Rarely, altered hemodynamic and hormonal changes during pregnancy may expand these benign lesions resulting in severe cord compression. The management of symptomatic vertebral hemangioma during pregnancy is controversial as modalities like radiotherapy and embolization are not suitable and surgery during pregnancy has a risk of preterm labor. Few cases of pregnancy related symptomatic vertebral hemangioma with marked epidural component have been reported in the literature. We report a case of 23-year-old primigravida who developed rapidly progressive paraparesis at 28 weeks of gestation and spine magnetic resonance imaging (MRI) revealed upper thoracic vertebral hemangioma with extensive extra-osseous extension and spinal cord compression. Laminectomy and surgical decompression of the cord was performed at 32 weeks of the pregnancy. There was significant improvement in muscle power after a week of surgery. Six weeks postoperatively she delivered a full term normal baby with subsequent improvement of neurologic deficit. Repeat MRI of dorsal spine performed at 3 months postoperatively showed reduced posterior and anterior epidural components of vertebral hemangioma.     

Evolutionary history of redox metal-binding domains across the tree of life

Oxidoreductases mediate electron transfer (i.e., redox) reactions across the tree of life and ultimately facilitate the biologically driven fluxes of hydrogen, carbon, nitrogen, oxygen, and sulfur on Earth. The core enzymes responsible for these reactions are ancient, often small in size, and highly diverse in amino acid sequence, and many require specific transition metals in their active sites. Here we reconstruct the evolution of metal-binding domains in extant oxidoreductases using a flexible network approach and permissive profile alignments based on available microbial genome data. Our results suggest there were at least 10 independent origins of redox domain families. However, we also identified multiple ancient connections between Fe₂S₂- (adrenodoxin-like) and heme- (cytochrome c) binding domains. Our results suggest that these two iron-containing redox families had a single common ancestor that underwent duplication and divergence. The iron-containing protein family constitutes ∼50% of all metal-containing oxidoreductases and potentially catalyzed redox reactions in the Archean oceans. Heme-binding domains seem to be derived via modular evolutionary processes that ultimately form the backbone of redox reactions in both anaerobic and aerobic respiration and photosynthesis. The empirically discovered network allows us to peer into the ancient history of microbial metabolism on our planet.Oxidoreductases are anciently derived enzymes that mediate electron transfer (i.e., redox) reactions across the tree of life and ultimately came to facilitate biologically driven fluxes of hydrogen, carbon, nitrogen, oxygen, and sulfur on Earth (1). It has been suggested that an ancestral pool of peptide modules may have given rise to the first protein folds that were dispersed into different superfamilies (2–4). Some of these peptide modules are part of the limited set of building blocks (i.e., the “redox enzyme construction kit”) that gave rise to many oxidoreductases (5). Given this Darwinian model of “descent with modification” for amino acid sequences in the active sites of enzymes, we analyzed a set of core of oxidoreductase catalytic domains to elucidate origin(s) and evolutionary patterns of biological electron transfer reactions.Previous analysis suggests that the catalytic domains evolved in microbes long before the Great Oxidation Event (GOE) ca. 2.4 billion y ago (6). However, owing to their ancient provenance, often small size, and high divergence, the evolutionary history of these domains is challenging to reconstruct. For example, a recent attempt to reconstruct the phylogeny of oxidoreductase domains based on structural data (7) was limited to pairwise distance analysis (without an underlying model of structure evolution) and implied a monophyletic origin of all metal-binding domains. To address the evolutionary history of oxidoreductases, we used hidden Markov model (HMM) (8–10) profile-to-profile alignments and protein similarity networks (11, 12) to study the metal-binding domains. HMMs (10) are a class of probabilistic models generally applicable to linear sequences (13). Because profile HMMs capture family-specific information, including functionally and structurally important residues, they are more sensitive and accurate than sequence alignments alone when searching for deeply diverged family members (2, 14, 15). The evolutionary relationships of protein families identified using profile HMMs may be reconstructed with similarity networks. These networks are composed of vertices (nodes), which represent protein sequences, connected by edges, representing similarity above a specified cutoff. Protein similarity networks offer an appealing alternative to phylogenetic approaches that rely on simultaneous multiple sequence alignments to reconstruct strictly bifurcating trees. By incorporating different metrics (e.g., pairwise alignment of profiles or sequence-to-profile alignments), network analysis provides a flexible approach to access the composition of domains in ancient protein families. In this study we applied a flexible network approach (11, 12) and permissive profile alignments (2, 14, 15) on microbial genome data to reconstruct the evolutionary history of oxidoreductase metal-binding domains. Our results suggest that whereas there were at least 10 independent origins of redox domain families one core family of iron-containing oxidoreductases came to dominate the electron fluxes across the planet before the evolution of oxygen. This family continues to represent the core of biologically catalyzed electron transfer reactions on Earth.