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Purpose. To review the results of patients who underwent arthroscopic reconstruction of the anterior cruciate ligament (ACL) via a single incision technique using a bone-patellar tendon-bone autograft. Methods. Patients with ACL-deficient knees who were symptomatic and wanted to maintain an active lifestyle or continue sporting activities were included. ACL reconstruction using the bone-patellar tendon-bone graft was performed on 100 patients. One-year follow-up was completed in 78 patients who were then reviewed. The mean age of patients reviewed was 26.8 years (range, 21–39 years), of whom 35 (44.9%) were aged between 26 and 30 years. There were 73 men and 5 women (ratio, 14.6:1). Injuries on the right side outnumbered those on the left (44 versus 34). Sports injuries accounted for 66.7% (n=52) of patients, motor vehicle accidents and household injuries accounted for 30.8% (n=24) and 2.6% (n=2), respectively. Results. Excellent and good-to-excellent results were achieved in 7 (9%) and 61 (78.2%) of patients. Residual anterior knee pain (n=18) was the most common complication, followed by difficulty in regaining full range of motion (n=10) and divergence of femoral screw (n=9). Conclusion. This procedure provides consistent and reproducible results in carefully selected patients and allows them an early return to sporting activities with minimal residual morbidity.

Abstract Patients with pancreatic cancer commonly develop weight loss and muscle wasting. Whether adipose tissue and skeletal muscle losses begin before diagnosis and the potential utility of such losses for earlier cancer detection are not well understood. We quantify skeletal muscle and adipose tissue areas from computed tomography (CT) imaging obtained 2 months to 5 years before cancer diagnosis in 714 pancreatic cancer cases and 1748 matched controls. Adipose tissue loss is identified up to 6 months, and skeletal muscle wasting is identified up to 18 months before the clinical diagnosis of pancreatic cancer and is not present in the matched control population. Tissue losses are of similar magnitude in cases diagnosed with localized compared with metastatic disease and are not correlated with at-diagnosis circulating levels of CA19-9. Skeletal muscle wasting occurs in the 1–2 years before pancreatic cancer diagnosis and may signal an upcoming diagnosis of pancreatic cancer.

Summary: Phosphomannomutase 2-congenital disorder of glycosylation (PMM2-CDG) is a rare inborn error of metabolism caused by deficiency of the PMM2 enzyme, which leads to impaired protein glycosylation. While the disorder presents with primarily neurological symptoms, there is limited knowledge about the specific brain-related changes caused by PMM2 deficiency. Here, we demonstrate aberrant neural activity in 2D neuronal networks from PMM2-CDG individuals. Utilizing multi-omics datasets from 3D human cortical organoids (hCOs) derived from PMM2-CDG individuals, we identify widespread decreases in protein glycosylation, highlighting impaired glycosylation as a key pathological feature of PMM2-CDG, as well as impaired mitochondrial structure and abnormal glucose metabolism in PMM2-deficient hCOs, indicating disturbances in energy metabolism. Correlation between PMM2 enzymatic activity in hCOs and symptom severity suggests that the level of PMM2 enzyme function directly influences neurological manifestations. These findings enhance our understanding of specific brain-related perturbations associated with PMM2-CDG, offering insights into the underlying mechanisms and potential directions for therapeutic interventions.

Introduction: Spondylodiscitis (SD) is an infection of the intervertebral disc with involvement of the adjacent vertebral bodies. Diagnostic tests with CT-guided biopsy only provide a positive yield in 14%–48% of cases. Percutaneous endoscopic debridement and drainage (PEDD) has recently shown promise in the treatment of spondylodiscitis. Research question: The purpose of this study is to determine differences in pathogen identification and clinical outcomes for PEDD versus CT-guided needle biopsy in SD patients. Materials and methods: We conducted a systematic review of the literature using PRISMA guidelines to determine differences in positive microbiology results, perioperative complications, pain control, and long-term clinical outcomes for PEDD vs. CT-guided needle biopsy in SD patients. Results: 1078 studies were evaluated, 87 of which underwent full review. 15 studies met the inclusion and exclusion criteria, including 7 PEDD, 7 CT-guided biopsy, and 1 CT-guided biopsy vs. PEDD article, for a total of 192 PEDD patients and 604 CT-guided biopsy patients. We found 36.59% of CT-guided biopsy patients had positive microbiology results, compared to 84.38% of PEDD patients. No major perioperative complications occurred as a result of the PEDD procedure. Of the five PEDD studies that reported pain outcomes, greater than 80% of patients experienced relief after intervention. Discussion and conclusion: These results suggest that PEDD may improve pathogen identification while simultaneously reducing pain compared to CT-guided needle biopsy in SD. Although current treatment guidelines recommend CT-guided biopsy, in patients with severe back pain and suspected SD, PEDD can be considered an alternative intervention.

Background Context: COVID-19 has been shown to adversely affect multiple organ systems, yet little is known about its effect on perioperative complications after spine surgery or the optimal timing of surgery after an infection. We used the NIH National COVID Cohort Collaborative (N3C) database to characterize the risk profile in patients undergoing spine surgery during multiple time windows following COVID-19 infection. Methods: We queried the National COVID Cohort Collaborative, a database of 17.4 million persons with 6.9 million COVID-19 cases, for patients undergoing lumbar spinal fusion surgery. Patients were stratified into those with an initial documented COVID-19 infection within 3 time periods: 0 to 2 weeks, 2 to 6 weeks, or 6 to 12 weeks before surgery. Results: A total of 60,541 patients who underwent lumbar spinal fusion procedures were included. Patients who underwent surgery within 2 weeks of their COVID-19 diagnosis had a significantly increased risk for venous thromboembolic events (OR 2.29, 95% CI 1.58–3.32), sepsis (OR 1.56, 95% CI 1.03–2.36), 30-day mortality (OR 5.55, 95% CI 3.53–8.71), and 1-year mortality (OR 2.70, 95% CI 1.91–3.82) compared with patients who were COVID negative during the same period. There was no significant difference in the rates of acute kidney injury or surgical site infection. Patients undergoing surgery between 2 and 6 weeks or between 6 and 12 weeks from the date of COVID-19 infection did not show significantly elevated rates of any complication analyzed. Conclusions: Patients undergoing lumbar spinal fusion within 2 weeks from initial COVID-19 diagnosis are at increased risk for perioperative venous thromboembolic events and sepsis. This effect does not persist beyond 2 weeks, however, so it may be warranted to postpone non-urgent spine surgeries for at least 2 weeks following a COVID-19 infection or to consider a more aggressive VTE chemoprophylaxis regimen for urgent surgery in COVID-19 patients.

The activity of multiple enzymes is dysregulated in cancer, but this cannot always be measured through enzyme expression. Here, the authors develop methods to measure protease activity across the organism, tissue, and single cell scales, and identify protease dysregulation in lung cancer and its response to targeted therapy.

Reactive microglia are observed with aging and in Lewy body disorders, including within the olfactory bulb of men with Parkinson's disease. However, the functional impact of microglia in these disorders is still debated. Resetting these reactive cells by a brief dietary pulse of the colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX5622 may hold therapeutic potential against Lewy-related pathologies. To our knowledge, withdrawal of PLX5622 after short-term exposure has not been tested in the preformed α-synuclein fibril (PFF) model, including in aged mice of both sexes. Compared to aged female mice, we report that aged males on the control diet showed higher numbers of phosphorylated α-synuclein+ inclusions in the limbic rhinencephalon after PFFs were injected in the posterior olfactory bulb. However, aged females displayed larger inclusion sizes compared to males. Short-term (14-day) dietary exposure to PLX5622 followed by control chow reduced inclusion numbers and levels of insoluble α-synuclein in aged males—but not females—and unexpectedly raised inclusion sizes in both sexes. Transient delivery of PLX5622 also improved spatial reference memory in PFF-infused aged mice, as evidenced by an increase in novel arm entries in a Y-maze. Superior memory was positively correlated with inclusion sizes but negatively correlated with inclusion numbers. Although we caution that PLX5622 delivery must be tested further in models of α-synucleinopathy, our data suggest that larger-sized—but fewer—α-synucleinopathic structures are associated with better neurological outcomes in PFF-infused aged mice.

Approaches to manage nonalcoholic fatty liver disease (NAFLD) are limited by an incomplete understanding of disease pathogenesis. The aim of this study was to identify hepatic gene‐expression patterns associated with different patterns of liver injury in a high‐risk cohort of adults with obesity. Using the NanoString Technologies (Seattle, WA) nCounter assay, we quantified expression of 795 genes, hypothesized to be involved in hepatic fibrosis, inflammation, and steatosis, in liver tissue from 318 adults with obesity. Liver specimens were categorized into four distinct NAFLD phenotypes: normal liver histology (NLH), steatosis only (steatosis), nonalcoholic steatohepatitis without fibrosis (NASH F0), and NASH with fibrosis stage 1‐4 (NASH F1‐F4). One hundred twenty‐five genes were significantly increasing or decreasing as NAFLD pathology progressed. Compared with NLH, NASH F0 was characterized by increased inflammatory gene expression, such as gamma‐interferon‐inducible lysosomal thiol reductase (IFI30) and chemokine (C‐X‐C motif) ligand 9 (CXCL9), while complement and coagulation related genes, such as C9 and complement component 4 binding protein beta (C4BPB), were reduced. In the presence of NASH F1‐F4, extracellular matrix degrading proteinases and profibrotic/scar deposition genes, such as collagens and transforming growth factor beta 1 (TGFB1), were simultaneously increased, suggesting a dynamic state of tissue remodeling. Conclusion: In adults with obesity, distinct states of NAFLD are associated with intrahepatic perturbations in genes related to inflammation, complement and coagulation pathways, and tissue remodeling. These data provide insights into the dynamic pathogenesis of NAFLD in high‐risk individuals.

Abstract Patients with Alagille syndrome carry monogenic mutations in the Notch signaling pathway and face complications such as jaundice and cholestasis. Given the presence of intrahepatic ductopenia in these patients, Notch2 receptor signaling is implicated in driving normal biliary development and downstream branching morphogenesis. As a result, in vitro model systems of liver epithelium are needed to further mechanistic insight of biliary tissue assembly. Here, primary human intrahepatic cholangiocytes as a candidate population for such a platform are systematically evaluated, and conditions that direct their branching morphogenesis are described. It is found that extracellular matrix presentation, coupled with mitogen stimulation, promotes biliary branching in a Notch‐dependent manner. These results demonstrate the utility of using 3D scaffolds for mechanistic investigation of cholangiocyte branching and provide a gateway to integrate biliary architecture in additional in vitro models of liver tissue.

Primaquine (PQ) is a widely used anti-malaria drug, but its mechanism of action is unclear. Here, Camarda et al. show that PQ’s activity against liver and sexual Plasmodium stages depends on generation of hydroxylated-PQ metabolites (OH-PQm), which, undergoing further reactions, results in production of H2O2.

Rotator cuff repairs are associated with suboptimal outcomes and possibly greater incidence of retears if the biological healing environment is compromised. Strategies to optimize tendon–bone healing include the use of bioinductive scaffolds and regenerative stem cell therapy. The subacromial bursa has been shown to have significant pluripotent stem cell potency for tendon healing and has the advantage of easy accessibility and no added cost. However, a reproducible surgical technique for bursal mobilization, harvest, and vascularity preservation has not been described. We describe our technique for vasculature-preserving bursal mobilization and harvest of the entire posterosuperior and lateral subacromial bursa, and its use in rotator cuff repair augmentation is presented. The technique involves mobilization of the bursa as a continuous layer by maintain its medial and lateral vascularity. The bursa is advanced laterally, and the “vascular bursal duvet” and cuff tendons are repaired together as a tendon–bursa unit.

Abstract Vestibular schwannoma (VS) is the most common tumor of the cerebellopontine angle, and it typically presents with sensorineural hearing loss. The genomic landscape of schwannoma is complex and many of the molecules implicated in VS pathogenesis represent targets not amenable to antibody-based or small molecule therapeutics. Tumor-targeted delivery of small interfering RNA (siRNA) therapeutics provides a direct and effective means to interrogate targets while minimizing off-target effects. To establish a preclinical model for therapeutic inhibition of putative targets in VS, archived tumor specimens, fresh tumor cells derived from patients with sporadic VS, and an established schwannoma cell line were screened. Nanoparticles directed by the tumor-homing peptide iRGD were selectively taken up by primary VS cultures in vitro via interactions with αvβ3/β5 integrins and neuropilin-1 (NRP-1). Cellular uptake was inhibited by a neutralizing antibody against αv integrin in a dose-dependent manner. When applied to primary VS cultures, iRGD-targeted nanoparticles delivered siRNA directed against TNFα in a receptor-specific fashion to potently silence gene expression and protein secretion. Taken together, our results provide a proof of principle for tumor-targeted, nanoparticle-mediated delivery of siRNA to VS and establish a novel platform for the development and pre-clinical screening of molecular therapeutics against VS.

Malaria eradication is a major goal in public health but is challenged by relapsing malaria species, expanding drug resistance, and the influence of host genetics on antimalarial drug efficacy. To overcome these hurdles, it is imperative to establish in vitro assays of liver-stage malaria for drug testing. Induced pluripotent stem cells (iPSC) potentially allow the assessment of donor-specific drug responses, and iPSC-derived hepatocyte-like cells (iHLCs) can facilitate the study of host genetics on host-pathogen interactions and the discovery of novel targets for antimalarial drug development. We establish in vitro liver-stage malaria infections in iHLCs using P. berghei, P. yoelii, P. falciparum, and P. vivax and show that differentiating cells acquire permissiveness to malaria infection at the hepatoblast stage. We also characterize antimalarial drug metabolism capabilities of iHLCs using prototypical antimalarial drugs and demonstrate that chemical maturation of iHLCs can improve their potential for antimalarial drug testing applications.

Osteoid osteoma has been reported infrequently around the elbow joint, and is usually treated with radiofrequency ablation or open excision. Elbow arthroscopy is useful for excision of accessible lesions, and the accompanying elbow stiffness can be treated concurrently. This report describes an arthroscopic excision of an osteoid osteoma located in the juxta-articular distal humeral bone. An initial adhesiolysis and capsulectomy is performed to gain access to the region above the capitellar articular margin. A 70° arthroscope is necessary to visualize this region via the anteromedial portal. An accessory lateral portal is used to detach the capsule from the distal humerus; the scar tissue overlying the lesion is debrided and the circumferential lesion is visualized and probed for identification of its extent. A biopsy is performed, and thereafter the lesion is excised piecemeal. The sclerotic margins are curetted, and radiofrequency ablation is performed. The technique is cosmetic and minimally invasive, and can be performed in revision scenarios involving recurrences after open surgery or needle radiofrequency thermal ablation. Early rehabilitation restores range of motion and strength. Technical tips for identification and curettage of the lesion are presented.

Proximal humerus fracture fixation may be complicated by persistent postsurgical stiffness or implant-related problems. Arthroscopic plate removal is a cosmetic and functionally beneficial procedure; however, the procedure is technically difficult in the presence of severe subdeltoid scarring. The technique described here shows an arthroscopic subdeltoid adhesiolysis and proximal humerus plate removal using systematic access to 5 regions of screw positions on the plate. After initial glenohumeral adhesiolysis, a thorough subacromial and subdeltoid bursectomy is performed. The axillary nerve and deltoid are retracted via an anterosuperolateral portal, and a posterolateral portal is used for panoramic viewing along the plate length. Lateral portals are placed above and below the axillary nerve, and these are used for screw removal. Finally, the plate is removed via a 1-inch incision along the previous surgical scar. The technique is cosmetic and minimally invasive, and early rehabilitation restores range of motion and strength. Technical tips for safe dissection in the scarred subdeltoid space and guidelines for protection of neurovascular structures are presented.

Displaced radial head fractures are treated with open reduction and internal fixation using implants. Failure of fixation may occur in the presence of comminution and in multifragmentary fractures; open surgical approaches are necessary for removal of the implants and radial head resection. Arthroscopic radial head resection has been described as a minimally invasive and effective treatment for failed radial head fracture fixation; however, periarticular adhesions and prominent implants add to the complexity and technical difficulty of the procedure. The described technique uses 3 portals for adhesiolysis, implant removal, and radial head resection. Resection is performed in stages; smaller-diameter instruments are used to gain and improve access, and larger resectors are used subsequently. Adequacy of resection is assessed arthroscopically and with biplanar imaging. The arthroscopic technique avoids the need for an open surgical approach and prevents subsequent morbidity. In addition, the rehabilitation time is shorter and patient satisfaction is high.

An acute perilunate wrist injury that is unreduced for more than 6 weeks results in severe disability, and even open reduction with stabilization through wide dorsal and volar approaches is technically challenging. This report describes an arthroscopic technique for reduction and percutaneous wire stabilization of a chronic perilunate wrist dislocations. The technique involves initial radiocarpal and midcarpal access through the 6R and 3-4 portals, and these portals are used for synovectomy and debridement of capsular flap tears. The midcarpal joint is accessed initially through the radiocarpal joint, and additional midcarpal portals are used for sequential perilunate adhesiolysis before carpal mobilization and reduction. A percutaneous wire drilled into the lunate is used as a joystick to manipulate the lunate into its anatomic alignment along the carpal bones, and percutaneous transcarpal wire fixation is performed to stabilize the carpus. Arthroscopic and fluoroscopic guidance is used to optimize anatomic reduction and to confirm stability. The wrist is immobilized for 6 weeks; the percutaneous wires are removed thereafter, and the wrist is mobilized. Overall, the arthroscopic technique provides a safe and reproducible method for treatment of this complex chronic injury.

Distal biceps rupture is associated with significant functional disability, and surgical treatment involves open or endoscopic-assisted repair of the ruptured tendon through an anterior incision. This report describes an endoscopic approach that is performed with 2 portals for visualization and instrumentation. Preoperative sonography is used to identify bony and soft-tissue landmarks. The viewing portal is a proximal anterolateral “parabiceps portal” developed by the author, and the landmarks and relevant anatomic relations have been derived from a preliminary anatomic study. The working portal is a distal anterior portal and permits access to the radial tuberosity through the internervous muscular plane. The parabiceps portal permits visualization of the anterior and medial region of the radial tuberosity. A detailed description of the endoscopic pathoanatomy of the distal biceps tendon region is presented. The distal anterior portal is used for retrieval of the ruptured tendon, and thereafter the tuberosity is debrided and anchors are placed under vision. The ruptured tendon is whipstitched and docked onto the tuberosity, and nonsliding knots are used to securely reattach the tendon to bone. Overall, the 2-portal technique provides a method for tendon repair under direct visualization and is safe and reproducible.

Chronic painful snapping scapula is characterized by inflammation and scarring of 1 or more bursae in the infraserratus space and is often refractory to conservative treatment. Surgical treatment involves excision of the bursae, as well as partial scapulectomy of the superomedial impinging region; both open and endoscopic approaches have been described with good results. Scapulothoracic endoscopy is technically difficult, and the potential complications can be serious. This report describes an endoscopic approach that can be performed with only 2 medial parascapular portals for visualization and instrumentation. The endoscopic anatomy of the infraserratus space is revisited, and 3 anatomic landmarks (serratus anterior, subspinous bursal curtain, and superomedial bony angle) are identified for safe dissection and intraoperative orientation. The surgical field is subdivided into 3 anatomic zones (superomedial space, subspinous space, and scapular bony angle), and the anatomic boundaries of these zones are demonstrated. The decompression procedure is subdivided into 4 stages (superomedial bursectomy, subspinous adhesiolysis, tuberoplasty, and scapuloplasty), and a measured resection technique for scapuloplasty is performed. The use of newer motorized rasps permits optimal bony resection, and additional portals are unnecessary. Overall, the step-by-step technique provides a methodical approach for safety, reproducibility, and optimization of the procedure.

Intraosseous ganglion cysts (IOGs) are uncommon lesions of the carpal bones and can present with persistent pain and stiffness of the wrist. Surgical decompression is recommended, and a variety of approaches to decompress symptomatic IOGs of the wrist have been described. We describe an arthroscopic approach that can be performed with only 2 portals and offers excellent access for visualization and instrumentation. The procedure involves creating a 3.2-mm tunnel into the lunate cyst; this is performed through the dorsal non-articular surface of the lunate, under direct vision, and the position is confirmed with fluoroscopy. A 2.4-mm arthroscope is passed through the drill hole, and a direct “cystoscopic” view of the IOG is obtained. Biopsy of the cyst contents is performed under direct vision, and small-joint shavers and burrs are used for effective debridement. Advantages of this technique are actual visualization of the pathology, complete intracystic debridement, and simultaneous treatment of any coexistent intra-articular pathology. In addition, the minimal 3.2-mm lunate tunnel access maintains the structural integrity of the lunate and reduces the need for additional bone graft supplementation.

The arthroscopic remplissage procedure is an effective addition to a standard anterior repair in traumatic anterior shoulder instability associated with large humeral defects. The double-barrel remplissage is an all–intra-articular technique that uses a double-pulley, sliding, and self-retaining knot mechanism called the double-barrel knot. A 70° arthroscope (posterior portal) is necessary for adequate visualization of the humeral defect and the rotator cuff. Trans-tendon anchors (single or double loaded) are inserted into the superior and inferior aspects of the humeral defect through a cannula that is placed posterior to the infraspinatus. Placement of anchors is facilitated by insertion of a guidewire, as well as an anchor sleeve that is threaded over it. The double-barrel knot is formed using the anchors as a double-pulley system, and the knot is tensioned after the anterior repair is complete. Intra-articular visualization confirms adequate approximation and compression of the infraspinatus tendon and capsule into the defect. Advantages include an increased surface area (footprint) for healing and ease of knotting without the necessity for additional subacromial dissection.

This study showing 65 percent hearing loss in cases of cleft lip and/or palate cases.

The complexity of micropatterned cell constructs has been limited by difficulties in patterning more than two surface components on a culture substrate. Photolithography using multiple aligned masks is well established for generalized multicomponent patterning, but is often too harsh for biomolecules. We report a two-mask photolithographic process that is tuned to preserve bioactivity in patterns composed of covalently coupled poly(ethylene glycol) (PEG), adsorbed extracellular matrix protein (e.g., collagen I), and adsorbed serum proteins (e.g., vitronectin). Thereby, we pattern two cell typesprimary hepatocytes and 3T3 fibroblastsdemonstrating control over contact and spacing (20−200 m) between the two cell types for over one week. This method is applicable to the study of intercellular communication in cell biology and tissue engineering. [ABSTRACT FROM AUTHOR]

We have developed a perfusion bioreactor system that allows the formation of steady state oxygen gradients in cell culture. In this study, gradients were formed in cultures of rat hepatocytes to study the role of oxygen in modulating cellular functions. A model of oxygen transport in our flat-plate reactor was developed to estimate oxygen distribution at the cell surface. Experimental measurements of outlet oxygen concentration from various flow conditions were used to validate model predictions. We showed that cell viability was maintained over a 24-h period when operating with a physiologic oxygen gradient at the cell surface from 76 to 5 mmHg O2 at the outlet. Oxygen gradients have been implicated in the maintenance of regional compartmentalized metabolic and detoxification functions in the liver, termed zonation. In this system, physiologic oxygen gradients in reactor cultures contributed to a heterogeneous distribution of phosphoenolpyruvate carboxykinase (predominantly localized upstream) and cytochrome P450 2B (predominantly localized downstream) that correlates with the distribution of these enzymes in vivo. The oxygen gradient chamber provides a means of probing the oxygen effects in vitro over a continuous range of O2 tensions. In addition, this system serves as an in vitro model of zonation that could be further extended to study the role of gradients in ischemia–reperfusion injury, toxicity, and bioartificial liver design. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 82: 253–262, 2003. [ABSTRACT FROM AUTHOR]

The temperature dependence of the electrical resistivity (r) and thermopower (S) of misfit cobaltite Ca3Co4O9 has been studied. The compound is a promising thermoelectric material, exhibiting very low r([?]1.3 × 10[?]4 O cm) and reasonably high S ([?]56 µV K[?]1) at room temperature, which is desirable for thermoelectric applications. At T < 80 K, S exhibits T3/2 dependence, suggesting that electron-magnon scattering has a pronounced influence on S at low temperatures. Ca3Co4O9 exhibits a temperature independent power factor in the temperature range 300-80 K. A comparison of the temperature dependence of the power factor of Ca3Co4O9 with various materials projected or used as a thermoelectric cooler (e.g. single crystal of short c-axis Ca3Co4O9, polycrystalline La0.95Sr0.05CoO3, Bi0.85 Sb0.15, Bi2Te3, Bi-SiO2 composite) indicates that title compound Ca3Co4O9 is a much superior candidate for thermoelectric applications. [ABSTRACT FROM AUTHOR]

Elbow bicipitoradial bursitis and partial distal biceps tendon (DBT) tears are a result of chronic overuse or other infective/inflammatory pathology and may be refractory to conservative treatment. The all-endoscopic approach provides minimally invasive access to the bursal space and DBT, and diagnostic and therapeutic procedures can be performed under direct endoscopic vision. The technique uses 2 portals, the proximal parabiceps portal and distal anterior portal, and the bursa is insufflated to create a working space. Tissue biopsies are obtained under direct endoscopic visualization, and debridement along 6 bursal zones can be effectively performed. An endoscopic probe test is demonstrated for assessment of partial DBT tears, and low-grade tears are debrided to stable tissue. The all-endoscopic technique is safe and reproducible, and it is a stepping-stone in the learning curve of all-endoscopic repair and reconstruction of distal biceps ruptures.

Background: In the past decade, there has been an increase in the number and types of bariatric procedures in India. It is, thus, important to monitor prevalent bariatric practices. Aim: To identify prevalent pre- and post-operative dietary practices by bariatric professionals across India. Materials and Methods: Data regarding various pre- and post-surgery dietary practices were collected using an Internet-based survey. Thirty-three bariatric professionals including dietitians (n = 25) and surgeons (n = 8) across the country participated in the survey. The data were analysed, and prevalent dietary practices were identified. Results: Five (20%) dietitians were not involved in the pre-surgery consultation. Nineteen (70%) professionals put all patients on a low-calorie pre-surgery diet regardless of their body mass index, with a preference (n = 21; 77.7%) for liquid diet. Twenty-three (70%) professionals put patients on post-surgery liquid diet for 1–2 weeks. Thereafter, 28 (84.8%) professionals recommended soft diet for 2–4 weeks. Twenty-seven (81%) professionals used protein shakes (as opposed to dietary sources) as their primary source of protein for the first 3 months post-surgery. Fourteen (36%) professionals stopped protein shake supplements within 6 months post-surgery. Ten (30%) professionals reported whey protein aversions in >25% of the patients. Twenty-three (71%) professionals advocated a meal with

Background: Respiratory tract infections represent a significant public health risk, and timely and accurate detection of bacterial infections facilitates rapid therapeutic intervention. Furthermore, monitoring the progression of infections after intervention enables ‘course correction’ in cases where initial treatments are ineffective, avoiding unnecessary drug dosing that can contribute to antibiotic resistance. However, current diagnostic and monitoring techniques rely on non-specific or slow readouts, such as radiographic imaging and sputum cultures, which fail to specifically identify bacterial infections and take several days to identify optimal antibiotic treatments. Methods: Here we describe a nanoparticle system that detects P. aeruginosa lung infections by sensing host and bacterial protease activity in vivo, and that delivers a urinary detection readout. One protease sensor is comprised of a peptide substrate for the P. aeruginosa protease LasA. A second sensor designed to detect elastases is responsive to recombinant neutrophil elastase and secreted proteases from bacterial strains. Findings: In mice infected with P. aeruginosa, nanoparticle formulations of these protease sensors—termed activity-based nanosensors (ABNs)—detect infections and monitor bacterial clearance from the lungs over time. Additionally, ABNs differentiate between appropriate and ineffective antibiotic treatments acutely, within hours after the initiation of therapy. Interpretation: These findings demonstrate how activity measurements of disease-associated proteases can provide a noninvasive window into the dynamic process of bacterial infection and resolution, offering an opportunity for detecting, monitoring, and characterizing lung infections. Fund: National Cancer Institute, National Institute of Environmental Health Sciences, National Institutes of Health, National Science Foundation Graduate Research Fellowship Program, and Howard Hughes Medical Institute. Keywords: Protease, Nanoparticle, Diagnostic, Bacterial pneumonia

Engineered liver systems come in a variety of platform models, from 2-dimensional cocultures of primary human hepatocytes and stem cell–derived progeny, to 3-dimensional organoids and humanized mice. Because of the species-specificity of many human hepatropic pathogens, these engineered systems have been essential tools for biologic discovery and therapeutic agent development in the context of liver-dependent infectious diseases. Although improvement of existing models is always beneficial, and the addition of a robust immune component is a particular need, at present, considerable progress has been made using this combination of research platforms. We highlight advances in the study of hepatitis B and C viruses and malaria-causing Plasmodium falciparum and Plasmodium vivax parasites, and underscore the importance of pairing the most appropriate model system and readout modality with the particular experimental question at hand, without always requiring a platform that recapitulates human physiology in its entirety.

In order to fulfill their evolutionary role as support cells, astrocytes have to tolerate intense oxidative stress under conditions of brain injury and disease. It is well known that astrocytes exposed to mild oxidative stress are preconditioned against subsequent stress exposure in dual hit models. However, it is unclear whether severe oxidative stress leads to stress tolerance, stress exacerbation, or no change in stress resistance in astrocytes. Furthermore, it is not known whether reactive astrocytes surviving intense oxidative stress can still support nearby neurons. The data in this Brief Report suggest that primary cortical astrocytes surviving high concentrations of the oxidative toxicant paraquat are completely resistant against subsequent oxidative challenges of the same intensity. Inhibitors of multiple endogenous defenses (e.g., glutathione, heme oxygenase 1, ERK1/2, Akt) failed to abolish or even reduce their stress resistance. Stress-reactive cortical astrocytes surviving intense oxidative stress still managed to protect primary cortical neurons against subsequent oxidative injuries in neuron/astrocyte co-cultures, even at concentrations of paraquat that otherwise led to more than 80% neuron loss. Although our previous work demonstrated a lack of stress tolerance in primary neurons exposed to dual paraquat hits, here we show that intensely stressed primary neurons can resist a second hit of hydrogen peroxide. These collective findings suggest that stress-reactive astroglia are not necessarily neurotoxic, and that severe oxidative stress does not invariably lead to stress exacerbation in either glia or neurons. Therefore, interference with the natural functions of stress-reactive astrocytes might have the unintended consequence of accelerating neurodegeneration.

Manipulation of the master regulator of energy homeostasis AMP-activated protein kinase (AMPK) activity is a strategy used by many intracellular pathogens for successful replication. Infection by most pathogens leads to an activation of host AMPK activity due to the energetic demands placed on the infected cell. Here, we demonstrate that the opposite is observed in cells infected with rodent malaria parasites. Indeed, AMPK activity upon the infection of hepatic cells is suppressed and dispensable for successful infection. By contrast, an overactive AMPK is deleterious to intracellular growth and replication of different Plasmodium spp., including the human malaria parasite, P. falciparum. The negative impact of host AMPK activity on infection was further confirmed in mice under conditions that activate its function. Overall, this work establishes the role of host AMPK signaling as a suppressive pathway of Plasmodium hepatic infection and as a potential target for host-based antimalarial interventions.

Background: Oral squamous cell carcinoma (OSCC) primarily spreads through direct invasion and/or lymphatic route. During the invasion, tumor cells break through the basement membrane, penetrate the connective tissue to interact with the extracellular matrix (ECM). An attempt was made to evaluate the connective tissue changes in different grades of OSCCs and their influence in predicting the biological behavior of these tumors. Materials and Methods: A total of 30 histologically proven cases comprising 5 normal mucosa, 10 well-differentiated OSCC's, 10 moderately differentiated OSCC's, and 5 poorly differentiated OSCC's were examined for the presence of any ECM changes by using special stains. Interpretation of staining intensity was carried out and statistically analyzed. Results: Van Gieson stain showed abundant thick collagen fibers, dispersed collagen fibers, thin few dispersed collagen fibers in well-, moderately- and poorly-differentiated OSCC's, respectively. Verhoeff's Van-Gieson showed negative staining for elastic fibers around tumor islands in different grades of OSCCs. PAS stain showed moderate staining for glycoprotein in well-differentiated OSCC and negative in moderately and poorly differentiated cases. Picrosirius red stain showed Type 1 collagen fibers in well and moderately differentiated OSCC cases and Type 3 collagen fibers in poorly differentiated cases. Conclusion: The observations of this study revealed altered staining reactions of the collagenous stroma and glycoproteins suggesting that tumor cells may release certain enzymes that play a role in the manipulation of ECM to enhance their own survival.

Homeostasis of mammalian cell function strictly depends on balancing oxygen exposure to maintain energy metabolism without producing excessive reactive oxygen species. In vivo, cells in different tissues are exposed to a wide range of oxygen concentrations, and yet in vitro models almost exclusively expose cultured cells to higher, atmospheric oxygen levels. Existing models of liver-stage malaria that utilize primary human hepatocytes typically exhibit low in vitro infection efficiencies, possibly due to missing microenvironmental support signals. One cue that could influence the infection capacity of cultured human hepatocytes is the dissolved oxygen concentration. We developed a microscale human liver platform comprised of precisely patterned primary human hepatocytes and nonparenchymal cells to model liver-stage malaria, but the oxygen concentrations are typically higher in the in vitro liver platform than anywhere along the hepatic sinusoid. Indeed, we observed that liver-stage Plasmodium parasite development in vivo correlates with hepatic sinusoidal oxygen gradients. Therefore, we hypothesized that in vitro liver-stage malaria infection efficiencies might improve under hypoxia. Using the infection of micropatterned co-cultures with Plasmodium berghei, Plasmodium yoelii or Plasmodium falciparum as a model, we observed that ambient hypoxia resulted in increased survival of exo-erythrocytic forms (EEFs) in hepatocytes and improved parasite development in a subset of surviving EEFs, based on EEF size. Further, the effective cell surface oxygen tensions (pO2) experienced by the hepatocytes, as predicted by a mathematical model, were systematically perturbed by varying culture parameters such as hepatocyte density and height of the medium, uncovering an optimal cell surface pO2 to maximize the number of mature EEFs. Initial mechanistic experiments revealed that treatment of primary human hepatocytes with the hypoxia mimetic, cobalt(II) chloride, as well as a HIF-1α activator, dimethyloxalylglycine, also enhance P. berghei infection, suggesting that the effect of hypoxia on infection is mediated in part by host-dependent HIF-1α mechanisms.

With the rate of spinal surgery increasing, we have seen a concomitant increase in the number of revision cases. It is, therefore, important to have a systematic approach to the management of these complicated patients with unique problems. A thorough understanding of the different pathologies affecting revision spine patients is critical to an effective treatment recommendation. Lateral access is a useful management approach since it can avoid the complications of operating through previous approaches. Furthermore, it possesses certain advantages for treatment in specific circumstances outlined in this paper. Long-term studies are needed to demonstrate the safety and efficacy of the lateral approach compared to the anterior and posterior approaches in the treatment of revision spine patients.

Cells organize in complex three-dimensional patterns by interacting with proteins along with the surrounding extracellular matrix. This organization provides the mechanical and chemical cues that ultimately influence a cell's differentiation and function. Here, we computationally investigate the pattern formation process of vascular mesenchymal cells arising from their interaction with Bone Morphogenic Protein-2 (BMP-2) and its inhibitor, Matrix Gla Protein (MGP). Using a first-principles approach, we derive a reaction-diffusion model based on the biochemical interactions of BMP-2, MGP and cells. Simulations of the model exhibit a wide variety of three-dimensional patterns not observed in a two-dimensional analysis. We demonstrate the emergence of three types of patterns: spheres, tubes, and sheets, and show that the patterns can be tuned by modifying parameters in the model such as the degradation rates of proteins and chemotactic coefficient of cells. Our model may be useful for improved engineering of three-dimensional tissue structures as well as for understanding three dimensional microenvironments in developmental processes.

Blood is a dense suspension of soft non-Brownian cells of unique importance. Physiological blood flow involves complex interactions of blood cells with each other and with the environment due to the combined effects of varying cell concentration, cell morphology, cell rheology, and confinement. We analyze these interactions using computational morphological image analysis and machine learning algorithms to quantify the non-equilibrium fluctuations of cellular velocities in a minimal, quasi-two-dimensional microfluidic setting that enables high-resolution spatio-temporal measurements of blood cell flow. In particular, we measure the effective hydrodynamic diffusivity of blood cells and analyze its relationship to macroscopic properties such as bulk flow velocity and density. We also use the effective suspension temperature to distinguish the flow of normal red blood cells and pathological sickled red blood cells and suggest that this temperature may help to characterize the propensity for stasis in Virchow's Triad of blood clotting and thrombosis.

The article cites a study focusing on the use of emergent electromagnetic properties of nanoparticle (NP) self assemblies in building new medical and biochemical assays with high sensitivity. The exploitation of NP has been made to probe for a host of pathological inputs in virto including DNA, RNA, proteins, viruses and enzymic activity. The researchers revealed the synthesis of NPs based on Boolean logic to monitor multiple biological processes associated with tumorigenesis.