IFN-λ3, not IFN-λ4, likely mediates IFNL3-IFNL4 haplotype-dependent hepatic inflammation and fibrosis

Genetic variation in the IFNL3-IFNL4 (interferon-λ3-interferon-λ4) region is associated with hepatic inflammation and fibrosis. Whether IFN-λ3 or IFN-λ4 protein drives this association is not known. We demonstrate that hepatic inflammation, fibrosis stage, fibrosis progression rate, hepatic infiltration of immune cells, IFN-λ3 expression, and serum sCD163 levels (a marker of activated macrophages) are greater in individuals with the IFNL3-IFNL4 risk haplotype that does not produce IFN-λ4, but produces IFN-λ3. No difference in these features was observed according to genotype at rs117648444, which encodes a substitution at position 70 of the IFN-λ4 protein and reduces IFN-λ4 activity, or between patients encoding functionally defective IFN-λ4 (IFN-λ4-Ser70) and those encoding fully active IFN-λ4-Pro70. The two proposed functional variants (rs368234815 and rs4803217) were not superior to the discovery SNP rs12979860 with respect to liver inflammation or fibrosis phenotype. IFN-λ3 rather than IFN-λ4 likely mediates IFNL3-IFNL4 haplotype-dependent hepatic inflammation and fibrosis

Simulating rewetting events in intermittent rivers and ephemeral streams: a global analysis of leached nutrients and organic matter

Climate change and human pressures are changing the global distribution and extent of intermittent rivers and ephemeral streams (IRES), which comprise half of the global river network area. IRES are characterized by periods of flow cessation, during which channel substrates accumulate and undergo physico‐chemical changes (preconditioning), and periods of flow resumption, when these substrates are rewetted and release pulses of dissolved nutrients and organic matter (OM). However, there are no estimates of the amounts and quality of leached substances, nor is there information on the underlying environmental constraints operating at the global scale. We experimentally simulated, under standard laboratory conditions, rewetting of leaves, riverbed sediments, and epilithic biofilms collected during the dry phase across 205 IRES from five major climate zones. We determined the amounts and qualitative characteristics of the leached nutrients and OM, and estimated their areal fluxes from riverbeds. In addition, we evaluated the variance in leachate characteristics in relation to selected environmental variables and substrate characteristics. We found that sediments, due to their large quantities within riverbeds, contribute most to the overall flux of dissolved substances during rewetting events (56‐98%), and that flux rates distinctly differ among climate zones. Dissolved organic carbon, phenolics, and nitrate contributed most to the areal fluxes. The largest amounts of leached substances were found in the continental climate zone, coinciding with the lowest potential bioavailability of the leached organic matter. The opposite pattern was found in the arid zone. Environmental variables expected to be modified under climate change (i.e. potential evapotranspiration, aridity, dry period duration, land use) were correlated with the amount of leached substances, with the strongest relationship found for sediments. These results show that the role of IRES should be accounted for in global biogeochemical cycles, especially because prevalence of IRES will increase due to increasing severity of drying events

Simulating rewetting events in intermittent rivers and ephemeral streams: A global analysis of leached nutrients and organic matter

Climate change and human pressures are changing the global distribution and the ex‐ tent of intermittent rivers and ephemeral streams (IRES), which comprise half of the global river network area. IRES are characterized by periods of flow cessation, during which channel substrates accumulate and undergo physico‐chemical changes (precon‐ ditioning), and periods of flow resumption, when these substrates are rewetted and release pulses of dissolved nutrients and organic matter (OM). However, there are no estimates of the amounts and quality of leached substances, nor is there information on the underlying environmental constraints operating at the global scale. We experi‐ mentally simulated, under standard laboratory conditions, rewetting of leaves, river‐ bed sediments, and epilithic biofilms collected during the dry phase across 205 IRES from five major climate zones. We determined the amounts and qualitative character‐ istics of the leached nutrients and OM, and estimated their areal fluxes from riverbeds. In addition, we evaluated the variance in leachate characteristics in relation to selected environmental variables and substrate characteristics. We found that sediments, due to their large quantities within riverbeds, contribute most to the overall flux of dis‐ solved substances during rewetting events (56%–98%), and that flux rates distinctly differ among climate zones. Dissolved organic carbon, phenolics, and nitrate contrib‐ uted most to the areal fluxes. The largest amounts of leached substances were found in the continental climate zone, coinciding with the lowest potential bioavailability of the leached OM. The opposite pattern was found in the arid zone. Environmental vari‐ ables expected to be modified under climate change (i.e. potential evapotranspiration, aridity, dry period duration, land use) were correlated with the amount of leached sub‐ stances, with the strongest relationship found for sediments. These results show that the role of IRES should be accounted for in global biogeochemical cycles, especially because prevalence of IRES will increase due to increasing severity of drying event

A global agenda for advancing freshwater biodiversity research

Global freshwater biodiversity is declining dramatically, and meeting the challenges of this crisis requires bold goals and the mobilisation of substantial resources. While the reasons are varied, investments in both research and conservation of freshwater biodiversity lag far behind those in the terrestrial and marine realms. Inspired by a global consultation, we identify 15 pressing priority needs, grouped into five research areas, in an effort to support informed stewardship of freshwater biodiversity. The proposed agenda aims to advance freshwater biodiversity research globally as a critical step in improving coordinated actions towards its sustainable management and conservation

A global agenda for advancing freshwater biodiversity research

Global freshwater biodiversity is declining dramatically, and meeting the challenges of this crisis requires bold goals and the mobilisation of substantial resources. While the reasons are varied, investments in both research and conservation of freshwater biodiversity lag far behind those in the terrestrial and marine realms. Inspired by a global consultation, we identify 15 pressing priority needs, grouped into five research areas, in an effort to support informed stewardship of freshwater biodiversity. The proposed agenda aims to advance freshwater biodiversity research globally as a critical step in improving coordinated actions towards its sustainable management and conservation.Peer reviewe

Revision Anterior Glenoid Reconstruction With Distal Tibia Allograft Combined With Open Capsular Shift

Background: Managing patients with recurrent anterior shoulder instability and glenoid bony deficiency remains a challenge. Multiple graft options, including iliac crest, distal clavicle, coracoid, and distal tibia allograft have been used. There is a growing body of evidence that supports distal tibia allograft for glenoid restoration in patients with shoulder instability due to its ability to restore the articular surface as well as the glenoid depth and curvature. Indications: Surgical indications for anterior glenoid reconstruction with distal tibia allograft combined with open capsular shift include patients with recurrent shoulder instability and glenoid bone loss. Technique Description: A deltopectoral interval is utilized and the subscapularis is split in lines with its fibers. The subscapularis and capsule are split together in a horizontal fashion and tagged together. Any prior hardware is then removed utilizing appropriate removal sets, a burr, and a broken screw set if necessary. The anterior glenoid is then prepared and the defect is measured. Bone marrow aspirate is then harvested from the proximal humerus using a vortex needle. The distal tibia allograft is then cut to size and prepared utilizing pulsed lavage, pressurized sterile carbon dioxide, and the bone marrow aspirate. The allograft is then fixed with solid stainless steel 3.5-mm cortical screws with washers. The medial, glenoid based capsular repair it completed by placing 1.8-mm knotless FiberTak anchor at the bottom of the distal tibia allograft. A free needle is utilized to place a horizontal mattress stitch from the anchor to the inferior capsule, which is then loaded onto a shuttling suture, to repair it to the anterior inferior glenoid. A knotless anchor is then placed right off the chondral margin of the humeral head, and this is used to repair both the capsule and subscapularis in the correct position by passing through both inferior and superior leaflets. This is then loaded onto the knotless anchor and reduced, which shifts the subscapularis and capsule laterally. The remainder of the subscapularis split is then closed. Patients are then placed in a sling with an abduction pillow with no shoulder range of motion for 6 weeks. They can then progress their therapy with a goal of returning to sport at 6 months. Results: Several large systemic reviews have shown that return to sport rates after anterior glenoid reconstruction range between 80% and 90%, with returning to the same level of play in the 70% range. Discussion: Anterior glenoid reconstruction utilizing distal tibia allograft combined with an open capsular shift is a durable surgical option for patients presenting with shoulder instability and glenoid bone loss. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication

Osteochondral Allograft Transplantation for the Unstable Capitellar Osteochondritis Dissecans Lesion: An Anconeus Preserving Approach

Background: Osteochondritis dissecans (OCD) of the capitellum can be a disabling condition that typically affects adolescent, overhead athletes. To date, a variety of different surgical treatment options have been described. Indications: Surgical indications for osteochondral allograft transplantation (OCA) for capitellar OCD lesions include failure of nonsurgical management or prior surgery and unstable, full-thickness lesions of almost any size affecting both bone and cartilage. The anconeus preserving approach specifically provides wide access to nearly the entire capitellum and can be used for lesions in almost any location. Technique Description: The anconeus preserving approach for OCA utilizes the interval between the anconeus and the ulna. With the patient positioned supine and the elbow flexed on an arm table, an incision is made approximately 1 cm lateral to the olecranon and is carried down to the fascia. Electric cautery is used to dissect the interval between the ulna and the anconeus. The anconeus is elevated off the ulna and retracted laterally to expose the underlying joint capsule. An L-shaped capsulotomy is performed over the center of the capitellum, just proximal to the annular ligament of the radial head. A pin is placed into the center of the lesion, perpendicular to the capitellum. A cannulated reamer 0.5 mm smaller than the lesion is used to ream the lesion to a depth of approximately 5 mm. Depth measurements are taken at all 4 poles of the defect. About 3 cc of bone marrow aspirate harvest is then obtained from the ulna using a cannulated needle. The oscillating saw is used to cut the graft to size using the prior measurements. The bone marrow aspirate is placed onto the osseous side of the graft before the osteochondral graft is impacted into the recipient site. The capsulotomy is then closed, and the anconeus is repaired back to the ulna. Postoperatively, patients begin range of motion as soon as tolerated, initiate strengthening at 6 weeks, and initiate return-to-sport programming at 3 months. Results: Lesions treated with OCA typically demonstrate improvement in all outcome measures, including functional scores, graft incorporation, articular surface congruity, and return-to-sport. Complications and graft failure is rare. Discussion/Conclusion: OCA using an anconeus preserving approach is a reliable option for surgical management of unstable OCD lesions. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication

Arthroscopic Rotator Cuff Repair With Superior Capsule Reconstruction for Irreparable Supraspinatus Tears

Background: Irreparable rotator cuff tears represent approximately 12% of all presenting cuff tears, and multiple surgical techniques have been described for treatment, including allograft/bridge augmentation, debridement, partial repair, subacromial balloon, tendon transfer, and superior capsule reconstruction (SCR). SCR has demonstrated durable improvement in range of motion (ROM) and outcome scores at 2 and 5 years. Indications: Surgical indications for SCR include an irreparable tear of the supraspinatus and/or infraspinatus with a preserved or reparable subscapularis and preserved glenohumeral joint cartilage. Technique Description: Diagnostic arthroscopy is performed to identify and characterize the rotator cuff tear. Thorough debridement of the greater tuberosity is performed. Two all-suture FiberTak anchors are placed in the superior aspect of the glenoid. Two 2.6-mm FiberTak suture anchors are placed in the humeral head at the chondral margin. After measuring, the dermal allograft is cut to size with 15-mm overhang left on the far lateral edge. A 12-mm passport cannula is inserted laterally and the sutures from the glenoid and humeral head anchors are brought out through the cannula maintaining their position and orientation. The sutures are passed through the graft outside the cannula. The graft is introduced into the shoulder via the passport cannula with a back grasper. A cannula-in-cannula technique is used to tie the glenoid anchors first and then the medial row anchors. Two lateral row swivel lock anchors are used to complete a standard double row repair. Margin convergence is performed between the dermal allograft and remaining rotator cuff anterior and posterior. Postoperatively, patients are kept in a sling for 6 weeks, with no shoulder ROM. From weeks 6 to 12, patients discontinue sling and begin passive progression to active ROM. Strengthening is initiated at 12 weeks, and return-to-sport or work is at approximately 6 months. Results: Irreparable rotator cuff tears treated with arthroscopic rotator cuff repair and SCR show durable improvement in patient-reported outcomes at 2 and 5 years. Re-tear rates did not differ between athletes and non-athletes. Discussion/Conclusion: Arthroscopic rotator cuff repair with SCR is a durable and reliable surgical option for patients presenting with preserved glenohumeral joint and irreparable supraspinatus and/or infraspinatus tear. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication

Correction to: At the US Epicenter of the COVID-19 Pandemic, an Orthopedic Residency Program Reorganizes.

[This corrects the article DOI: 10.1007/s11420-020-09765-5.]