COVID-19 Cases, Hospitalizations, and Deaths Among American Indian or Alaska Native Persons - Alaska, 2020-2021.

American Indian or Alaska Native (AI/AN) persons across the United States face substantial health disparities, including a disproportionately higher incidence of COVID-19 (1,2). AI/AN persons living in Alaska also face serious health and health care challenges, including access to care because 90% of the state's land area is inaccessible by road (3), and approximately one half of the state's AI/AN population (AI/AN race alone or in combination with another race) live in remote rural areas (4). To examine the extent of COVID-19-associated disparities among AI/AN persons living in Alaska, a retrospective analysis of COVID-19 cases reported to the Alaska Department of Health and Social Services (AKDHSS) during March 12, 2020-December 31, 2021, was conducted. The age-adjusted COVID-19 incidence among AI/AN persons was 26,583 per 100,000 standard population, approximately twice the rate among White persons living in Alaska (11,935). The age-adjusted COVID-19-associated hospitalization rate among AI/AN persons was 742 per 100,000, nearly three times the rate among White persons (273) (rate ratio [RR] = 2.72). The age-adjusted COVID-19-related mortality rate among AI/AN persons was 297 per 100,000, approximately three times that among White persons (104; RR = 2.86). Culturally competent public health efforts that are designed in collaboration with AI/AN persons and communities, including support for vaccination and other proven COVID-19 prevention strategies, are critical to reducing COVID-19-associated disparities among AI/AN persons in Alaska.

Reversed flow lateral circumflex femoral vessels as recipients for free fibular grafting in treatment of femoral head osteonecrosis.

Free fibular bone grafting is an effective treatment for early osteonecrosis of the femoral head in young patients. However, recipient vessels are often small rendering microvascular anastomosis difficult. We have developed a novel technique using retrograde flow through the branches of the lateral circumflex femoral artery to use the proximal end of the artery as the recipient vessel. A vessel diameter of up to 5 mm is obtained providing a good match with the peroneal vessels. We used this technique to perform vascularized bone grafting of the femoral head in 10 patients with Ficat grade 2 and 3 osteonecrosis. Pulsatile retrograde flow from the lateral circumflex femoral artery was observed in each case. Retrospective review gave a median follow up of 52 months (range 17-99). Symptoms improved in all 10 cases. There was no radiological deterioration over the period of follow-up in eight cases. One patient underwent conversion to a total hip replacement 24 months after surgery. These results compare favorably with other studies. The lateral circumflex femoral artery turnover technique is a reliable and useful technique in vascularized bone grafting of the femoral head.

Knoll and Sediment Drift near Hudson Canyon.

A parallel-bedded accumulation of sediments forms a low ridge on the upcurrent side of a partially moated knoll. These sediments were deposited beneath a southwestward-flowing current where it is locally decelerated by the obstructing knoll.

Variation in dermcidin expression in a range of primary human tumours and in hypoxic/oxidatively stressed human cell lines.

Dermcidin acts as a survival factor in a variety of cancer cell lines under hypoxia or oxidative stress. The aim of this study was to evaluate dermcidin expression in cell lines following simulation of tumour microenvironmental conditions and in a range of primary tumours. Tumour tissues were collected from patients with oesophageal (28 samples), gastric (20), pancreatic (five), bile duct (one) and prostatic (52) carcinomas as well as 30 benign tissue samples, for assessment of dermcidin mRNA levels using real-time PCR. Dermcidin expression was assessed in prostatic and pancreatic cancer cell lines, with and without induction of hypoxia or oxidative stress. Dermcidin mRNA expression was very low or absent in both unstressed and stressed prostate cell lines. None of the primary prostate tissue, benign or malignant, expressed dermcidin mRNA. Only two (4%) of the gastro-oesophageal cancer samples expressed moderate quantities of dermcidin mRNA. However, three (60%) of the pancreatic cancer samples and the single cholangiocarcinoma specimen had moderate/high levels of dermcidin expression. Of the two pancreatic cancer cell lines, one expressed dermcidin moderately but neither showed a response to hypoxia or oxidative stress. Expression of dermcidin in human primary tumours appears highly variable and is not induced substantially by hypoxia/oxidative stress in cell line model systems. The relationship of these findings to dermcidin protein levels and cell survival remains to be determined.

The posterior auricular muscle: a useful anatomical landmark for otoplasty.

BACKGROUND: The correct anatomical placement of conchomastoid sutures during suture otoplasty can sometimes prove challenging. If the suture vector is inaccurate, reduction can be difficult and this may lead to malrotation of the pinna. METHODS: This paper describes the adoption of the auricularis posterior muscle, which runs from the mastoid to the concha and whose function is to adduct the pinna, as a marker for conchomastoid suture placement. RESULTS AND CONCLUSION: The muscle is easily identified and dissected, providing a landmark for the placement of sutures onto the adjacent concha and mastoid fascia. This allows for an anatomical reduction of the pinna. It is believed that this approach will prove useful to the otoplasty surgeon.

Thigh burns from exploding e-cigarette lithium ion batteries: First case series.

E-cigarette (EC) use has risen meteorically over the last decade. The majority of these devices are powered by re-chargeable lithium ion batteries, which can represent a fire hazard if damaged, over-heated, over-charged or stored inappropriately. There are currently no reports in the medical literature of lithium ion battery burns related to EC use and no guidance on the appropriate management of lithium ion battery associated injuries. We report two individual cases of burn resulting from explosion of EC re-chargeable lithium ion batteries. Both patients required in-patient surgical management. We provide evidence that lithium ion battery explosions can be associated with mixed thermal and alkali chemical burns, resulting from the significant discharge of thermal energy and the dispersal of corrosive lithium ion compounds. We would recommend, as with other elemental metal exposures, caution in exposing lithium ion battery burns to water irrigation. Early and thorough cleaning and debridement of such burns, to remove residual lithium contamination, may limit the risk of burn wound extension and potentially improve outcomes.

Biophysical characterization of the catalytic domain of guanine nucleotide exchange factor BopE from Burkholderia pseudomallei.

BopE is a type III secreted protein from Burkholderia pseudomallei, the aetiological agent of melioidosis. Like its Salmonella homologues SopE and SopE2, BopE is a guanine nucleotide exchange factor for Rho GTPases. It is thought that, in order to be secreted by the type III system, proteins must be unfolded or only partially folded. As part of a study of B. pseudomallei virulence proteins, we have expressed, purified and characterized the catalytic domain of BopE (amino acids 78-261). Analytical ultracentrifugation experiments in conjunction with analytical size exclusion chromatography show that BopE(78-261) is monomeric in aqueous solution. CD spectroscopy indicates that the protein is predominantly alpha-helical, with predicted secondary structure composition of 59% alpha-helix and 7% beta-strand. NMR spectroscopy confirms that BopE(78-261) adopts a single, stable conformation. In differential scanning calorimetry experiments, thermal denaturation of BopE(78-261) (T(m) 52 degrees C) is reversible. Also, the secondary structure composition of BopE(78-261) changes little over a range of pH values from 3.5 to 10.5. BopE may therefore fold spontaneously to a functional form upon secretion into the host cell cytoplasm, and retains a native or native-like fold in varied environments. These properties are likely to be advantageous for a secreted bacterial effector protein.

Considerations in the surgical use of the flexor sheath and pulley system.

The use of the digital flexor sheath to reconstruct damaged structures in the fingers is an intriguing but under-investigated subject. The sheath is anchored firmly to the phalanges and palmar plates and has well-vascularized outer and synovial inner layers. The middle layer is strong and fibrous and not all of it is required for its main biomechanical function of maintaining the moment arm of the flexor tendons. These characteristics have led to several descriptions of different reconstructive uses. In sheath reconstruction, flaps can be used to repair damaged A2 and A4 pulleys. As an anchor, the sheath is useful for tenodeses and tendon transfers. It has been used in the correction of ulnar claw and swan neck deformities. In ligament reconstruction, the A1 pulley has been used to reconstruct the transverse intermetacarpal ligament in cleft hand and ray amputations. The sheath has also been used to cover tendon repairs and periosteal defects with the aim of decreasing adhesions. There is potential for further use of the flexor sheath in reconstructive surgery. The digital flexor sheath can be used to restore various finger functions providing its physiological roles are recognized and preserved. This review considers the different techniques described and their potential uses.

Arterial injuries at the elbow carry a high risk of muscle necrosis and warrant urgent revascularisation.

INTRODUCTION: Revascularisation following axial arterial system injury is effective in upper limb salvage but necrosis of muscle, the tissue most sensitive to ischaemia, may still occur. We examined the frequency of necrosis, its related factors and its functional significance. METHODS: The clinical findings and operative management of 13 patients with injuries at the elbow referred to 2 plastic surgical hand surgery units over a 30-month period were reviewed. Good outcome was defined as minimal impairment with return to previous occupation, intermediate outcome as moderate impairment with change in occupation and poor outcome as major functional loss preventing work. RESULTS: Seven patients injured the brachial and six injured both the radial and ulnar arteries. Concomitant injuries were severe with nerve injuries in 11 and muscle damage in 12 patients. Functional outcome was good in four cases, intermediate in four and poor in five. Muscle necrosis developed in four brachial artery injuries. In all four cases, initial successful revascularisation failed post-operatively. Case review revealed delayed recognition in three cases where pain heralded ischaemia but distal skin circulation and pulses were adequate. Of patients with necrosis, three had a poor outcome and one had an intermediate outcome. CONCLUSIONS: The risk of muscle necrosis must be considered when managing these injuries, particularly if initial revascularisation is unsuccessful. Every effort should be made to optimise repair technique and post-operative monitoring. Limb salvage is no longer enough. Fully viable muscle is necessary to restore function and livelihoods.

Dermcidin expression in hepatic cells improves survival without N-glycosylation, but requires asparagine residues.

Proteolysis-inducing factor, a cachexia-inducing tumour product, is an N-glycosylated peptide with homology to the unglycosylated neuronal survival peptide Y-P30 and a predicted product of the dermcidin gene, a pro-survival oncogene in breast cancer. We aimed to investigate whether dermcidin is pro-survival in liver cells, in which proteolysis-inducing factor induces catabolism, and to determine the role of potentially glycosylated asparagine residues in this function. Reverse cloning of proteolysis-inducing factor demonstrated approximately 100% homology with the dermcidin cDNA. This cDNA was cloned into pcDNA3.1+ and both asparagine residues removed using site-directed mutagenesis. In vitro translation demonstrated signal peptide production, but no difference in molecular weight between the products of native and mutant vectors. Immunocytochemistry of HuH7 cells transiently transfected with V5-His-tagged dermcidin confirmed targeting to the secretory pathway. Stable transfection conferred protection against oxidative stress. This was abrogated by mutation of both asparagines in combination, but not by mutation of either asparagine alone. These findings suggest that dermcidin may function as an oncogene in hepatic as well as breast cells. Glycosylation does not appear to be required, but the importance of asparagine residues suggests a role for the proteolysis-inducing factor core peptide domain.

Identification of a bacterial factor required for actin-based motility of Burkholderia pseudomallei.

Burkholderia pseudomallei is a Gram-negative facultative intracellular pathogen that enters and escapes from eukaryotic cells using the power of actin polymerization. We have identified a bacterial protein (BimA) that is required for the ability of B. pseudomallei to induce the formation of actin tails. BimA contains proline-rich motifs and WH2-like domains and shares limited homology at the C-terminus with the Yersinia autosecreted adhesin YadA. BimA is located at the pole of the bacterial cell at which actin polymerization occurs and mutation of bimA abolished actin-based motility of the pathogen in J774.2 cells. Transient expression of BimA in HeLa cells resulted in F-actin clustering reminiscent of that seen on WASP overexpression. Antibody-mediated clustering of a CD32 chimera in which the cytoplasmic domain was replaced with BimA resulted in localization of the chimera to the tips of F-actin enriched membrane protrusions. We report that purified truncated BimA protein binds monomeric actin in a concentration-dependent manner in cosedimentation assays and that BimA stimulates actin polymerization in vitro in a manner independent of the cellular Arp2/3 complex.

Actin-binding proteins from Burkholderia mallei and Burkholderia thailandensis can functionally compensate for the actin-based motility defect of a Burkholderia pseudomallei bimA mutant.

Recently we identified a bacterial factor (BimA) required for actin-based motility of Burkholderia pseudomallei. Here we report that Burkholderia mallei and Burkholderia thailandensis are capable of actin-based motility in J774.2 cells and that BimA homologs of these bacteria can restore the actin-based motility defect of a B. pseudomallei bimA mutant. While the BimA homologs differ in their amino-terminal sequence, they interact directly with actin in vitro and vary in their ability to bind Arp3.

Latent effects of fibronectin, alpha5beta1 integrin, alphaVbeta5 integrin and the cytoskeleton regulate pancreatic carcinoma cell IL-8 secretion.

Interactions between tumour cells and the microenvironment are increasingly recognised to have an influence on cancer progression. In pancreatic carcinoma, a highly desmoplastic stroma with abnormal extracellular matrix (ECM) protein and interleukin-8 (IL-8) expression is seen. To investigate whether the ECM may further contribute to abnormalities in the microenvironment by influencing IL-8 secretion, we cultured the Mia PaCa2 pancreatic carcinoma cell line on fibronectin. This resulted in a dose-dependent increase in IL-8 secretion, which was RGD dependent and accompanied by cell spreading and proliferation. The role of spreading was assessed by disruption of the cytoskeleton with cytochalasin D, resulting in a large increase in IL-8 secretion, which was reduced from 31- to 24-fold by fibronectin. This remarkable response was associated with inhibition of spreading and proliferation and represents a novel cytoskeletal function. To investigate whether it could be accounted for by the loss of integrin-mediated signalling, the expressed alpha5beta1, alphaVbeta5 and alpha3beta1 integrins were inhibited. alpha5beta1 inhibition prevented spreading and proliferation but produced a much smaller rise in IL-8 secretion than cytochalasin D. alphaVbeta5 inhibition alone had only minor effects but when inhibited in combination with alpha5beta1 completely abolished the response to fibronectin. These results reveal latent stimulatory effects of the alphaVbeta5 integrin on IL-8 secretion and suggest that integrin crosstalk may limit the induction of IL-8 secretion by fibronectin. However, the magnitude of IL-8 secretion induced by cytochalasin cannot be accounted for by integrin signalling and may reflect the influence of another signalling pathway or a novel, intrinsic cytoskeletal function.

Effect of a eutectic mixture of local anaesthetic agents (EMLA) on tourniquet pain in volunteers.

We studied the effects of EMLA on tourniquet pain in 10 healthy male volunteers. The tourniquet inflation time which was tolerated was significantly longer with EMLA (46.4 (SEM 3.5) min) compared with placebo (37.5 (2.7) min) (P less than 0.05). Linear analogue pain scores increased in both groups over the study period, but were significantly less in the EMLA group at 40 min (P less than 0.05). We conclude that tourniquet pain has a significant cutaneous component.

Cardiovascular and plasma catecholamine responses at tracheal extubation.

The haemodynamic responses to tracheal extubation at the end of surgery were compared with those occurring at tracheal intubation in 12 patients undergoing major elective surgery. Arterial cannulation was performed and heart rate (HR), systolic arterial pressure (SAP) and diastolic arterial pressure (DAP) were measured before induction of anaesthesia, before tracheal intubation, at the end of surgery and 1, 3 and 5 min after tracheal extubation. Laryngoscopy was avoided at the end of surgery. At all but the first of these stages, venous blood was obtained for measurement of plasma concentrations of adrenaline and noradrenaline. Rate-pressure product (RPP) was derived from SAP x HR. After tracheal intubation there were significant (P less than 0.05) increases in HR, DAP, RPP and in plasma concentrations of both adrenaline and noradrenaline. After extubation, only HR and adrenaline concentration at 5 min after extubation increased significantly compared with measurements at the end of surgery.

An Inv/Mxi-Spa-like type III protein secretion system in Burkholderia pseudomallei modulates intracellular behaviour of the pathogen.

Burkholderia pseudomallei is the causative agent of melioidosis, a serious infectious disease of humans and animals that is endemic in subtropical areas. B. pseudomallei is a facultative intracellular pathogen that may invade and survive within eukaryotic cells for prolonged periods. After internalization, the bacteria escape from endocytic vacuoles into the cytoplasm of infected cells and form membrane protrusions by inducing actin polymerization at one pole. It is believed that survival within phagocytic cells and cell-to-cell spread via actin protrusions is required for full virulence. We have studied the role of a putative type III protein secretion apparatus (Bsa) in the interaction between B. pseudomallei and host cells. The Bsa system is very similar to the Inv/Mxi-Spa type III secretion systems of Salmonella and Shigella. Moreover, B. pseudomallei encodes proteins that are very similar to Salmonella and Shigella Inv/Mxi-Spa secreted proteins required for invasion, escape from endocytic vacuoles, intercellular spread and pathogenesis. Antibodies to putative Bsa-secreted proteins were detected in convalescent serum from a melioidosis patient, suggesting that the system is functionally expressed in vivo. B. pseudomallei mutant strains lacking components of the Bsa secretion and translocation apparatus were constructed. The mutant strains exhibited reduced replication in J774.2 murine macrophage-like cells, an inability to escape from endocytic vacuoles and a complete absence of formation of membrane protrusions and actin tails. These findings indicate that the Bsa type III secretion system plays an essential role in modulating the intracellular behaviour of B. pseudomallei.

A Burkholderia pseudomallei type III secreted protein, BopE, facilitates bacterial invasion of epithelial cells and exhibits guanine nucleotide exchange factor activity.

We report the characterization of BopE, a type III secreted protein that is encoded adjacent to the Burkholderia pseudomallei bsa locus and is homologous to Salmonella enterica SopE/SopE2. Inactivation of bopE impaired bacterial entry into HeLa cells, indicating that BopE facilitates invasion. Consistent with this notion, BopE expressed in eukaryotic cells induced rearrangements in the subcortical actin cytoskeleton, and purified BopE exhibited guanine nucleotide exchange factor activity for Cdc42 and Rac1 in vitro.