Search

Copyright of Revista Ciencias de la Salud is the property of Colegio Mayor de Nuestra Senora del Rosario and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aims: This study aims to describe a new method that may be used as a supplement to evaluate humeral rotational alignment during intramedullary nail (IMN) insertion using the profile of the perpendicular peak of the greater tuberosity and its relation to the transepicondylar axis. We called this angle the greater tuberosity version angle (GTVA)., Methods: This study analyzed 506 cadaveric humeri of adult patients. All humeri were CT scanned using 0.625 × 0.625 × 0.625 mm cubic voxels. The images acquired were used to generate 3D surface models of the humerus. Next, 3D landmarks were automatically calculated on each 3D bone using custom-written C++ software. The anatomical landmarks analyzed were the transepicondylar axis, the humerus anatomical axis, and the peak of the perpendicular axis of the greater tuberosity. Lastly, the angle between the transepicondylar axis and the greater tuberosity axis was calculated and defined as the GTVA., Results: The value of GTVA was 20.9° (SD 4.7°) (95% CI 20.47° to 21.3°). Results of analysis of variance revealed that females had a statistically significant larger angle of 21.95° (SD 4.49°) compared to males, which were found to be 20.49° (SD 4.8°) (p = 0.001)., Conclusion: This study identified a consistent relationship between palpable anatomical landmarks, enhancing IMN accuracy by utilizing 3D CT scans and replicating a 20.9° angle from the greater tuberosity to the transepicondylar axis. Using this angle as a secondary reference may help mitigate the complications associated with malrotation of the humerus following IMN. However, future trials are needed for clinical validation., Competing Interests: The authors have no conflicts of interest to disclose., (© 2024 Gutierrez-Naranjo et al.)

Purpose: Malalignment of distal tibia fractures can lead to malunion/nonunion or alter the limb mechanical axis which may cause arthritis. Proposed methods to decrease malalignment include fibular fixation or multiplanar interlocking screws, however these remain controversial. This study aimed to identify factors associated with malalignment in distal tibial fractures with associated fibular shaft fractures., Methods: A retrospective review was performed of distal tibia fractures with associated fibular shaft fractures treated with intramedullary nailing at two level one trauma centers between 2015 and 2019. Cases involving malalignment (> 5° of deviation from anatomic axis on either coronal/sagittal axis) on final follow-up (minimum three months postoperatively) were compared to those without malalignment with regard to demographics, fracture characteristics, intraoperative characteristics, and complications., Results: The rate of malalignment was 13%. On multivariate analysis, multiplanar distal interlocking screw fixation (odds ratio [OR], 0.18; 95% confidence interval [CI] 0.03-0.92) was associated with a decreased rate of final malalignment, while nail diameter > 10 mm was associated with a higher rate (OR, 4.05; 95% CI 1.25-13.11). Fibular fixation was not associated with malalignment., Conclusion: Multiplanar distal interlocking screws may protect against malalignment. Fibula fixation does not appear associated with a decreased rate of malalignment in distal tibia fractures treated with intramedullary nails., Level of Evidence: III., (© 2024. The Author(s).)

Uncontrolled use of pesticides has caused a dramatic reduction in the number of pollinators, including bees. Studies on the effects of pesticides on bees have reported effects on both metabolic and neurological levels under chronic exposure. In this study, variations in the differential expression of head and thorax-abdomen proteins in Africanized A. mellifera bees treated acutely with sublethal doses of glyphosate and imidacloprid were studied using a proteomic approach. A total of 92 proteins were detected, 49 of which were differentially expressed compared to those in the control group (47 downregulated and 2 upregulated). Protein interaction networks with differential protein expression ratios suggested that acute exposure of A. mellifera to sublethal doses of glyphosate could cause head damage, which is mainly associated with behavior and metabolism. Simultaneously, imidacloprid can cause damage associated with metabolism as well as, neuronal damage, cellular stress, and impairment of the detoxification system. Regarding the thorax-abdomen fractions, glyphosate could lead to cytoskeleton reorganization and a reduction in defense mechanisms, whereas imidacloprid could affect the coordination and impairment of the oxidative stress response., (© 2024. The Author(s).)

Objective: To review and update the literature regarding outcomes following surgical management of chronic, grade III posterolateral corner (PLC) injuries, with an emphasis on estimating failure rates based upon objective parameters in light of the 2019 expert consensus, while secondarily comparing the failure rates of anatomic versus non-anatomic reconstruction techniques., Methods: A literature search was performed using the PubMed, Embase, MEDLINE, and Cochrane Library databases. Inclusion criteria consisted of level I-IV human clinical studies reporting subjective and objective outcomes in patients following surgical management for chronic (>6 weeks from injury) grade III PLC injuries, with a minimum two-year follow-up. The criterion for objective surgical failure was based on post-operative varus stress radiographs and defined as a side-to-side difference of 3 ​mm or more of lateral gapping., Results: A total of six studies, consisting of 10 separate cohorts encompassing a total of 230 patients, were identified. PLC reconstruction was performed in all cohorts, with 80 ​% (n ​= ​8/10) of these cohorts utilising an anatomic reconstruction technique. A failure rate ranging from 4.3 ​% to 36 ​% was found. Subgroup analysis revealed a failure rate of 4.3 ​%-24.2 ​% for anatomic reconstruction techniques, whereas a 0 ​%-36 ​% failure rate was found for non-anatomic reconstruction. Arthrofibrosis was the most common complication (range, 0 ​%-12.1 ​%) following surgery. 0 ​%-8 ​% of patients required revision PLC surgery., Conclusion: PLC reconstruction yields a wide variability in failure rates according to the side-to-side difference of 3 ​mm or more of lateral gapping on post-operative varus stress radiographs, with low revision rates following anatomic and non-anatomic reconstruction techniques., Level of Evidence: IV; Systematic Review of Level III and IV studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Case: A 34-year-old man was a restrained passenger involved in a high-speed rollover motor vehicle crash. The patient sustained a type 5 AC joint separation, severely comminuted intra-articular glenoid fracture with extension to the coracoid process base, displaced open scapular body fracture, a posterior shoulder dislocation of the glenohumeral joint, and a 2-part proximal humerus fracture., Conclusion: To our knowledge, this is the first report describing this injury pattern involving the superior shoulder suspensory complex with an associated open proximal humerus fracture-dislocation., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSCC/C357)., (Copyright © 2024 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated.)

Study Design: Case report and literature review., Objective: To report the relatively rare complication of delayed infection after cervical disc arthroplasty (CDA)., Background: Delayed infection of the M6 device has been a rarely reported complication, with all cases described outside of the United States. The reliability of positive intraoperative cultures remains an ongoing debate., Methods: Cases were reviewed, and findings were summarized. A literature review was performed and discussed, with special consideration to current reports of delayed M6 infection, etiology, and utility of intraoperative cultures., Results: We present a case of delayed infection 6 years after primary 1-level CDA with the M6 device. At revision surgery, gross purulence was encountered. Intraoperative cultures finalized with Staphylococcus epidermidis and Cutibacterium acnes. The patient was revised with removal of the M6 and conversion to anterior cervical discectomy and fusion. A prolonged course of intravenous antibiotics was followed by an oral course for suppression. At the final follow-up, the patient's preoperative symptoms had resolved., Conclusion: Delayed infection after CDA is a rare complication, with ongoing debate regarding the reliability of positive cultures. We describe an infected M6 and demonstrate the utility of implant removal, conversion to anterior cervical discectomy and fusion, and long-term antibiotics as definitive treatment., Level of Evidence: Level V-case report and literature review., Competing Interests: F.M.P. and M.W.C. are paid consultants for a company involved in the manufacturing of a device examined in this study. The remaining authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The purpose of this current concepts review is to highlight the evaluation and workup of hamstring injuries, nonoperative treatment options, and surgical decision-making based on patient presentation and injury patterns. Hamstring injuries, which are becoming increasingly recognized, affect professional and recreational athletes alike, commonly occurring after forceful eccentric contraction mechanisms. Injuries occur in the proximal tendon at the ischial tuberosity, in the muscle belly substance, or in the distal tendon insertion on the tibia or fibula. Patients may present with ecchymoses, pain, and weakness. Magnetic resonance imaging remains the gold standard for diagnosis and may help guide treatment. Treatment is dictated by the specific tendon(s) injured, tear location, severity, and chronicity. Many hamstring injuries can be successfully managed with nonoperative measures such as activity modification and physical therapy; adjuncts such as platelet-rich plasma injections are currently being investigated. Operative treatment of proximal hamstring injuries, including endoscopic or open approaches, is traditionally reserved for 2-tendon injuries with >2 cm of retraction, 3-tendon injuries, or injuries that do not improve with 6 months of nonoperative management. Acute surgical treatment of proximal hamstring injuries tends to be favorable. Distal hamstring injuries may initially be managed nonoperatively, although biceps femoris injuries are frequently managed surgically, and return to sport may be faster for semitendinosus injuries treated acutely with excision or tendon stripping in high-level athletes., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: O.A.O. has received support for education from Medwest Associates. J.C. has received consulting fees from Arthrex, CONMED Linvatec, Ossur, Smith & Nephew, DePuy Synthes Products, and Vericel and hospitality payments from Stryker and Medical Device Business Services. S.J.N. has received research support from Allosource, Arthrex, Athletico, DJ Orthopedics, Linvatec, Miomed, Smith & Nephew, and Stryker; consulting fees from Stryker and Ossur; IP royalties from Ossur and Stryker; and publishing royalties and consulting fees from Springer. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Background: The resurgence of Mycobacterium tuberculosis (Mtb) strains that resist anti-tuberculosis (anti-TB) drugs used currently stresses the search for more effective low-toxicity drugs against new targets. Due to their role in ion homeostasis and virulence, Mtb plasma membrane P-type ATPases are interesting anti-TB targets, in particular, the Ca 2+ transporting P2-type ATPase CtpF which is involved in oxidative stress response and persistence., Methods: In this study, the effect on the transcription level of the ctpF gene and other Mtb P2-type ATPases of two anti-Mtb hits was assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Both anti-Mtb hits ZINC14541509 and ZINC63908257 had been previously identified using pharmacophore-based virtual screening and MM-GBSA binding free energy. In addition, the bacterial activity of both compounds on Mycobacterium bovis was evaluated to see whether or not there is an effect on other mycobacteria of the Mtb complex., Results: qRT-PCR experiments showed that the ctpF transcription level was significantly higher in the presence of both compounds, especially ZINC14541509, strongly suggesting that CtpF may be a specific target of the selected compound., Conclusions: ZINC14541509 should be considered as an alternative for the structural-based design of novel anti-TB drugs., Competing Interests: None

Background: Direct-acting antivirals (DAA) were introduced to Latin America with the aim of eliminating hepatitis C (HCV) in the region. There are scarce data on the outcomes of people living with HIV and HCV treated with these medications in Colombia. This study compares the outcomes of patients with HIV-HCV co-infection and HCV mono-infection treated with DAAs., Methods: Retrospective observational study including patients ≥18 years old with HCV infection treated with DAAs from August 2017 to December 2019 in a comprehensive center in Colombia. The main outcome was sustained virologic response (SVR). Secondary outcomes included reinfection, relapse and adverse events., Results: We included 223 individuals with HCV treated with DAAs; 142 (63.6%) individuals were mono-infected and 81 (36.3%) co-infected. Genotypes 1b (49.7%) and 4 (33.9%) were the most common. Overall SVR after DAA treatment was 96.8%. Relapse rate was 2.24%, reinfection rate was 6.28% and adverse events occurred in 27.8% of cases. SVR was comparable in patients with co- and mono-infection (95% vs 97.8%, p=0.245)., Conclusion: DAA were effective in mono-infected (HCV) and co-infected (HCV/HIV) patients and reinfection was high in this last group., Competing Interests: Conflict of interests The authors have no conflict of interests to declare.

Purpose: To evaluate reported clinical outcomes and complications following radiofrequency (RF) ablation for the treatment of knee chondral lesions., Methods: A literature search was performed according to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines by querying EMBASE, PubMed, and Scopus computerized databases from database inception through October 2022. Level I to IV clinical studies that reported outcomes or complications following RF-based chondroplasty were included. Postoperative outcome scores and complications were aggregated. Study quality was assessed via the Newcastle-Ottawa Scale., Results: Ten articles from 2002 to 2018 consisting of 1,107 patients (n = 1,504 lesions) were identified. Four studies were of Level I evidence, 3 studies were Level II, 1 study was Level III, and 2 studies were Level IV. The mean patient age was 41.8 ± 6.3 years (range, 12-87). Seven studies (n = 1,037 patients) used bipolar RF devices, and 3 studies (n = 70 patients) used monopolar RF devices. The overall mean postoperative Lysholm, Tegner, and IKDC scores ranged from 83 to 91, 3.8 to 7, and 49 to 90, respectively, in lesions ranging from grade I-IV according to the Outerbridge Classification. Monopolar RF devices reported qualitatively similar mean changes in Lysholm scores (83), Tegner scores (3.8), and IKDC scores (range, 49-69) compared with bipolar RF devices (range, 86.4-91, 4.5-7, 90, respectively). The incidence of complications ranged from 0% to 4%. The most commonly reported complication was osteonecrosis (range, 0% to 4%). The incidence rate of patients undergoing additional surgery ranged from 0% to 4.5%., Conclusions: The available literature on RF-based chondroplasty shows its efficacy and safety for the treatment of knee chondral lesions, with good clinical outcome scores and low complication and reoperation rates., Level of Evidence: Level IV, systematic review of Level I-IV studies., (© 2023 The Authors.)

Purpose: To systematically examine the effects of radiofrequency (RF) ablation or coblation (controlled ablation) on chondrocyte viability following knee chondroplasty in preclinical literature to determine the effectiveness and safety of RF-based techniques., Methods: A literature search was performed in September 2022 using PubMed and Scopus using the following search terms combined with Boolean operators: "chondroplasty," "radiofrequency," "thermal," "knee," "chondral defect," "articular cartilage," and "cartilage." The inclusion criteria consisted of preclinical studies examining the effect of RF ablation or coblation on chondrocytes during knee chondroplasty. Exclusion criteria consisted of studies reporting chondroplasty in joints other than the knee, clinical studies, in vitro studies using animal models, case reports, non-full-text articles, letters to editors, surveys, review articles, and abstracts. The following data were extracted from the included articles: author, year of publication, chondral defect location within the knee and chondral characteristics, RF probe characteristics, cartilage macroscopic description, microscopic chondrocyte description, and extracellular matrix characteristics., Results: A total of 17 articles, consisting of 811 cartilage specimens, were identified. The mean specimen age was 63.4 ± 6.0 (range, 37-89) years. Five studies used monopolar RF devices, 7 studies used bipolar RF devices, whereas 4 studies used both monopolar and bipolar RF devices. Time until cell death during ablation at any power was reported in 5 studies (n = 351 specimens), with a mean time to cell death of 54.4 seconds (mean range, 23.1-64) for bipolar RF and 56.3 seconds (mean range, 12.5-64) for monopolar RF devices. Chondrocyte cell death increased with increased wattage, while treatment time was positively correlated with deeper cell death., Conclusions: In this systematic review, histologic analysis demonstrated that RF-based chondroplasty creates a precise area of targeted chondrocyte death, with minimal evidence of necrosis outside the target zone. Caution must be exercised when performing RF-based chondroplasty due to the risk of cell death with increased application time and wattage., Clinical Relevance: Although RF ablation has demonstrated favorable results in preliminary trials, including smoother cartilage and less damage to the surrounding healthy tissue, the risks versus benefits of the procedure are largely unknown. Caution must be exercised when performing RF-based chondroplasty in the clinical setting due to the risk of cell death with increased application time and wattage., (© 2023 The Authors.)

Oral dosage forms with adjustable drug release profiles were prepared using progesterone (PGR) as a poorly-soluble model drug. The dosage forms were made as stack assemblies of functional modules. The modules were made as PGR-carrying HPMC films cut into wafer-like circular pieces. Two types of modules were used in the study; one exhibited comparatively fast drug release and the other slow release. The fast vs. slow release of each type of film utilized resulted from the grade of HPMC used in each case. Drug loading in the assembly was controlled through the total number of modules. By adjusting the proportions of the two types of modules, it is possible to fine-tune the drug release rate of the multi-layer assemblies to a wide range of profiles, bracketed between a high and low end, corresponding to the inherently fastest or slowest release obtainable with the specific materials and procedures employed. This procedure is suitable for adjusting the spring-and-parachute parameters for enhancing/optimizing the bioavailability of poorly-soluble drugs, and for developing patient-centric formulations.

Purpose: To compare clinical and radiologic outcomes following superior capsular reconstruction (SCR) using dermal allograft versus tensor fascia lata (TFL) autograft for massive rotator cuff tears with a minimum 2-year follow-up., Methods: A literature search was performed by querying Scopus, EMBASE, and PubMed computerized databases from database inception through September 2022 in accordance with the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies evaluating clinical and radiologic outcomes, as well as complications following SCR for the treatment of massive rotator cuff tears were included. Study quality was assessed via the Newcastle-Ottawa Scale and the National Institutes of Health Quality Assessment. The mean change from preoperative to postoperative values (delta) was calculated for each outcome., Results: Seventeen studies, consisting of 519 patients were identified. Mean duration of follow-up ranged from 24 to 60 months. Mean reduction in visual analog scale pain score ranged from 2.9 to 5.9 points following use of dermal allograft, and 3.4 to 7.0 points following TFL autograft reconstruction. Mean improvements in American Shoulder and Elbow Surgeons score were similar between groups (dermal allograft: 28.0-61.6; TFL autograft: 24.7-59.3). The mean increase in forward flexion ranged from 31° to 38° with dermal allograft, versus 19° to 69° with TFL autograft. Average improvement in active external rotation with dermal allograft ranged from -0.4° to 11° and from 2° to 22.4° using TFL autograft. A similar change in acromiohumeral distance following SCR (dermal allograft: 0.9-3.2 mm; TFL autograft: 0.3-3.6 mm) was appreciated. The rate of complications within the dermal allograft group ranged from 4.5% to 38.2% versus 13.3% to 86.4% following TFL autograft. Failure rate ranged from 4.5 to 38.2% following dermal allograft versus 4.5 to 86.4% with TFL autograft., Conclusions: Acellular dermal allograft versus TFL autograft for SCR both demonstrate improved VAS and American Shoulder and Elbow Surgeons scores, with increased values in flexion and external rotation, and increased visual analog scale, although with high variability. Both grafts demonstrate high rates of complications and failures at minimum 2-year follow-up., Level of Evidence: IV; systematic review of level II-IV studies., (Copyright © 2023. Published by Elsevier Inc.)

Fungal infections have increased in recent decades with considerable morbidity and mortality, mainly in immunosuppressed or admitted-to-the-ICU patients. The fungal resistance to conventional antifungal treatments has become a public health problem, especially with Candida that presents resistance to several antifungals. Therefore, generating new alternatives of antifungal therapy is fundamental. One of these possibilities is the use of antimicrobial peptides, such as LL-37, which acts on the disruption of the microorganism membrane and promotes immunomodulatory effects in the host. In this study, we evaluated the in vitro antifungal activity of the LL-37 analogue peptides (AC-1, LL37-1, AC-2, and D) against different Candida spp. and clinical isolates obtained from patients with vulvovaginal candidiasis. Our results suggest that the peptides with the best ranges of MICs were LL37-1 and AC-2 (0.07 µM) against the strains studied. This inhibitory effect was confirmed by analyzing the yeast growth curves that evidenced a significant decrease in the fungal growth after exposure to LL-37 peptides. By the XTT technique we observed a significant reduction in the biofilm formation process when compared to yeasts untreated with the analogue peptides. In conclusion, we suggest that LL-37 analogue peptides may play an important antimicrobial role against Candida spp.

Background: Treatment of elbow instability remains challenging despite advancements in surgical techniques. The objective of this study was to evaluate obesity, advanced age or frailty, and altered cognitive function (because of mental handicap, stroke, dementia, or traumatic brain injury) as unique indications for the use of the internal joint stabilizer (IJS) to augment surgical treatment of elbow instability., Methods: This was a retrospective review of all patients 18 years and older with elbow instability who were managed with an IJS along with standard measures of care for their specific injury, such as fracture fixation and collateral ligament reconstruction. Patients were excluded if they did not have a minimum follow-up of 3 months. All patients were treated by a single shoulder and elbow fellowship-trained orthopedic traumatologist at an urban university-based level 1 trauma center., Results: Twenty-two patients were included in the study. Five patients were 60 years of age or older. Nine patients had a body mass index of 30 or greater. Five patients had a history of 1 or more cerebral insults or cognitive impairment. The majority of patients (21/22; 95%) regained elbow stability after the index surgery. At last follow-up, 14 of 22 patients (63%) regained a functional arc of motion, defined as at least 100° arc of motion, and 77% of patients had at least 90° of motion. Complications requiring revision surgery included culture-negative recurrent elbow instability (n = 1), deep infection (n = 1), and IJS failure without recurrent instability (n = 1). The IJS was removed in all 3 cases. Twelve patients underwent delayed IJS removal >2 months after the index surgery to grant additional time for bony and ligamentous healing and to permit secondary contracture release at the time of IJS removal. No complications were seen from delayed IJS removal., Conclusion: The IJS may be used to create elbow stability in complex patients, regardless of weight, frailty, cognitive function, neurologic insult, or other comorbidities. Unlike external fixation, the IJS does not require pin site care and is relatively light and low-profile. When augmenting surgical fixation for elbow instability, the IJS may be preferable for patients with complex comorbidities or social dynamics., (Copyright © 2022 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Background: Septic arthritis of the native shoulder is traditionally diagnosed with the same strategies as knee or hip septic arthritis. However, septic arthritis of the shoulder is frequently a missed or delayed diagnosis. Reliance on aspiration and serum markers has been called into question recently. The purpose of this study was to conduct a systematic review investigating the value of joint aspiration and serum markers in the diagnosis of native shoulder joint sepsis., Methods: PubMed/MEDLINE, Scopus, and the Cochrane Library were used in the systematic literature search from January 1, 1960, through January 23, 2021. The primary outcome was to report on the synovial white cell count of patients with native shoulder sepsis. Descriptive statistics using percentages, means, and intraclass correlation coefficient (ICC) values were used to summarize the results., Results: Thirty-one studies, including 25 case series, one case-control, and five cohort studies with a total of 7434 native shoulder joints, were included. There was no standardized approach to diagnosing septic arthritis of the shoulder. Only 10 studies (32%) reported on synovial white cell count with the majority yielding aspiration counts greater than 50,000 cells/mm 3 , although one study was as low as 30,000 cells/mm 3 ., Conclusions: The diagnosis of native shoulder joint sepsis lacks uniformity. Methods used to evaluate shoulder sepsis are heterogeneous and may lead to delays or misdiagnosis with devastating sequelae. Synovial white cell count is underutilized and may also present with a lower value than expected, which is likely related to the time interval between symptom onset and diagnosis., (© 2022. The Author(s).)

This review paper on femoral neck fractures in the elderly provides updated information from the most recent literature and examines the advantages and disadvantages of different surgical treatment options. Femoral neck fractures are a common injury that many orthopaedic surgeons will encounter within their practice. These injuries are associated with significant morbidity, and the economic impact of surgically fixing these fractures is notable. Contemporary treatment options include internal fixation, hemiarthroplasty, and total hip arthroplasty. For non-displaced fractures, both internal fixation and hemiarthroplasty remain feasible options. Hemiarthroplasty decreases re-operation rate, while internal fixation decreases operative time, blood loss, and infection risk. Newly designed fixation constructs require further investigation. For displaced fractures, the literature strongly supports arthroplasty. Most elderly patients with displaced femoral neck fractures should be managed with a hemiarthroplasty. In select active elderly patients, total hip arthroplasty may achieve favourable early functional outcomes as compared to a hemiarthroplasty. Finally, cemented arthroplasty decreases periprosthetic fracture risk as compared to cementless arthroplasty. However, experienced arthroplasty surgeons with significant expertise in press-fitting techniques may achieve similar outcomes with cementless arthroplasty., (© 2022. The Author(s) under exclusive licence to SICOT aisbl.)

The main goal of treatment for chronically unreduced elbow dislocations is to restore a stable, concentric joint and regain a satisfactory arc of motion. Due to the conflicting goals of restoring elbow stability and regaining a good arc of motion, the treatment of chronic elbow dislocation remains a challenge for even the experienced orthopedic surgeon. The standard treatment of these dislocations consists of open reduction, V-Y muscleplasty of the triceps, and temporary arthrodesis or cast immobilization. However, prolonged postoperative immobilization may result in elbow stiffness, which significantly limits the functional outcome. We present our surgical technique with a focus on restoring stable reduction such that early motion can be instituted and complications of prolonged immobilization can be avoided. From position to wound closure, surgical steps are presented in detail, with pearls for practice and a discussion on chronic elbow dislocation. The internal joint stabilizer is a safe and effective implant that complements the management of chronic elbow dislocations. This reproducible surgical technique allows for stability and early mobility while having the added benefit of circumventing complications associated with prolonged immobilization and hinged external fixation. Understanding the surgical indications, as well as the nuances of the surgical technique utilizing the internal joint stabilizer, is critical in order to improve patient outcomes and avoid complications., (© 2022 The Author(s).)

Objectives: To analyze the current incidence of postoperative infection for OTA/AO type C fractures of the tibial plateau and tibial plafond., Data Sources: Three medical databases: PubMed/MEDLINE, ScienceDirect, and the Cochrane Library, were used in our systematic literature search. Search results were restricted to articles transcribed in English/Spanish and publication date after January 1, 2000, to present day., Study Selection: Inclusion criteria were studies reporting postoperative infection data for OTA/AO type 41C, 43C, or equivalent fractures of skeletally mature individuals. A minimum of 6 total fractures of interest and a frequency of 75% overall were required. Studies reporting on pathologic fractures, stress fractures, or low-energy fracture types were excluded., Data Extraction: Two authors independently screened abstracts, evaluated full-text manuscripts, and extracted relevant data from included studies. Any instances of discrepancy were resolved within the study committee by consensus., Data Synthesis: Outcomes were expressed using direct proportions (PR) with a 95% confidence interval. The effects of comorbidities on infection rates were reported using odds ratios with a 95% confidence interval. All analyses used a DerSimonian-Laird estimate with a random-effects model based on heterogeneity. The presence of publication bias was evaluated using funnel plots and Egger's tests., Conclusions: Patients with these specific fractures develop infections at a notable frequency. The rates of deep infections were approximately 6% in tibial plateau fractures and 9% in tibial plafond fractures. These results may be useful as a reference for patient counseling and other future studies aimed at minimizing postoperative infection for these injuries., Level of Evidence: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: B. A. Zelle has consulted for 3M KCI Inc, USA and DepuySynthes and received compensation. B. A. Zelle has also received speaker fees from AO North America. B. A. Zelle has received research grants from DepuySynthes, 3M KCI Inc, Department of Defense, and the Orthopaedic Trauma Association. B. A. Zelle has received educational grants from AO North America, Arthrex, COTA, and Smith and Nephew Inc. He serves on the editorial boards of Brazilian Journal of Orthopaedics, International Orthopaedics, Journal of Bone and Joint Surgery, Journal of Orthopaedic Trauma, and Patient Safety in Surgery. None of these activities are related to the content of this article. The remaining authors report no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Plating midshaft clavicle fractures anteriorly is gaining popularity because of low complication rates. Improvements in plate fixation constructs for midshaft clavicle fractures have unclear clinical significance. The purpose of this study was to present the early clinical and radiographic outcomes of pre-contoured titanium anterior plates for the treatment of midshaft clavicle fractures., Methods: Skeletally mature patients who underwent plate fixation of a midshaft clavicular fracture from 2008 to 2015 using pre-contoured titanium anterior plates were included in this retrospective investigation. The primary outcome measures were union rate and hardware removal rate. The secondary outcome measures included reoperation for all causes and mechanical implant failure., Results: A total of 26 patients were included. Complete healing occurred in 96% of patients without further surgical intervention, and all patients achieved union. Medical complications occurred in 2 patients (7.7%), consisting of cellulitis (n = 1) and chronic pain (n = 1). In 1 patient (3.8%), delayed union occurred and the use of a bone stimulator was required postoperatively to achieve union. Finally, 2 patients (7.7%) had symptomatic implants that required removal., Conclusions: In the acute fracture setting, the anterior plating system used in this study led to a high rate of union with decreased rates of implant irritation. Only 7.7% of patients required hardware removal for symptomatic hardware, as opposed to the estimated 20%-60% reported in the literature in patients with symptomatic superior clavicle plates., (Copyright © 2021 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Macro- and micronutrients play important roles in the biological wound-healing pathway. Although deficiencies may potentially affect orthopaedic trauma patient outcomes, data on nutritional deficiencies in orthopaedic trauma patients remain limited in the literature. The purpose of this study was to (1) evaluate the prevalence of macro- and micronutrient deficiencies in orthopaedic trauma patients with lower extremity fractures and (2) evaluate the impact of such deficiencies on surgical site complications. This retrospective study identified 867 patients with lower extremity fractures treated with surgical fixation from 2019 to 2020. Data recorded included albumin, prealbumin, protein, vitamins A/C/D, magnesium, phosphorus, transferrin and zinc, as well as wound complications. Nutritional deficiencies were found for prealbumin, albumin and transferrin at 50.5%, 23.4% and 48.5%, respectively. Furthermore, a high prevalence of micronutrient deficiencies (vitamin A, 35.4%; vitamin C, 54.4%; vitamin D, 75.4%; and zinc, 56.5%) was observed. We also recorded a statistically significant difference in wound complications in patients who were deficient in prealbumin (21.6% vs. 6.6%, p = 0.0142) and vitamin C (56.8% vs. 28.6%, p = 0.0236). Our study outlines the prevalence of nutritional deficiencies in an orthopaedic trauma population and identifies areas for possible targeted supplementation to decrease wound complications.

Purpose: To evaluate if income status affects the timing of presentation to orthopaedic care, surgical treatment, or continuity of care following a closed ankle fracture., Methods: Th is retrospective study identified 434 patients with closed ankle fractures treated with operative fixation from 2014 to 2016. Median income data were extracted using the patients' ZIP codes and data from the U.S. Census Bureau., Results: Lower-income patients presented to the hospital and received surgical treatment significantly later than others. They were also more often uninsured and nonadherent with postoperative weightbearing precautions. Additionally, these patients less frequently sought care on the day of their injury, and they had both shorter inpatient stays and duration of overall follow-up in comparison with others., Conclusion: Socioeconomic status is a vital consideration for improving patient access to acute orthopaedic surgical care. Lower-income patients are more susceptible to multiple time-sensitive delays in their care, and these patients frequently encounter difficulties maintaining appropriate follow-up carex.

Carotid atherosclerotic plaque rupture can lead to cerebrovascular accident (CVA). By comparing RNA-Seq data from vascular smooth muscle cells (VSMC) extracted from carotid atheroma surgically excised from a group of asymptomatic and symptomatic subjects, we identified more than 700 genomic variants associated with symptomatology ( p < 0.05). From these, twelve single nucleotide polymorphisms (SNPs) were selected for further validation. Comparing genotypes of a hospital-based cohort of asymptomatic with symptomatic patients, an exonic SNP in the BIRC6 ( BRUCE / Apollon ) gene, rs35286811, emerged as significantly associated with CVA symptomatology ( p = 0.002; OR = 2.24). Moreover, BIRC6 mRNA levels were significantly higher in symptomatic than asymptomatic subjects upon measurement by qPCR in excised carotid atherosclerotic tissue ( p < 0.0001), and significantly higher in carriers of the rs35286811 risk allele ( p < 0.0001). rs35286811 is a proxy of a GWAS SNP reported to be associated with red cell distribution width (RDW); RDW was increased in symptomatic patients ( p < 0.03), but was not influenced by the rs35286811 genotype in our cohort. BIRC6 is a negative regulator of both apoptosis and autophagy. This work introduces BIRC6 as a novel genetic risk factor for stroke, and identifies autophagy as a genetically regulated mechanism of carotid plaque vulnerability.

COVID-19, a global pandemic causing to date more than 50 million cases and more than a million deaths, has to be controlled. SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) was identified as the causative agent. Controversy about this virus origin and infectious mechanism for adapting to humans remains a matter for discussion. Among all strategies for obtaining safe and potent vaccines, approaches based on attenuated-killed virus and non-replicating RNA viral vectors are demonstrating promising results. However, specificity of viral components targeted by human antibodies so far has not been demonstrated. A consistent strategy for obtaining functional-active antigens from SARS-CoV-2 specific ligands lead us to propose and test a number of synthetic components. From hundreds of starting sequences only fifteen fulfilled the design requirements and were produced as monomer and polymer forms and immuno-chemically tested. The design was based on worldwide representative reported virus genomes. A bioinformatics scheme by conventional methods and knowledge on MHC-I and II antigen processing mechanisms and HLA haplotype-restriction was performed including sensitive and resistant human populations to virus infection. Covid-19 patients' sera reactivity for synthetic SARS-CoV-2-designed components have proven a high recognition of specific molecules, as well as some evidence for a long-lasting humoral immune response.

Objectives: To describe the learning curve of pedicle screw placement using robot-assisted spine surgery of an experienced neurosurgeon and 2 supervised neurosurgical fellows., Methods: The first 120 cases of robot-assisted spine surgery at our institution were assessed. Patient variables included age, body mass index, and indication for surgery. Intraoperative variables included the vertebral level of screw placement, number of screws placed by each operator, intraoperative blood loss, and operative time. Postoperative variables included length of stay, discharge disposition, 30-day readmissions, wound complications, and hardware revisions. Screw accuracy was determined with image overlay analysis comparing planned screw trajectory on the navigation software with the intraoperative computed tomography scan with final screw placement. Two-dimensional accuracy was determined for the tip of the screw, tail of the screw, and angle at the screw was placed. The supervising physician and first fellow began utilizing the robot concurrently upon its arrival, and the second fellow began using the robot after the system had been in place for 7 months., Results: Both experienced surgeon and first fellow displayed a learning curve and achieved statistically significant improvement of accuracy after 30 screws. The second fellow had significantly better accuracy than the experienced surgeon in his first 30 screws. There were no complications from hardware placement in either group. There were no returns to the operating room for hardware issues., Conclusions: Robot-assisted spine surgery is a safe, accurate method of pedicle screw instrumentation. Our data show similar learning adaptation rates for the first fellow and the experienced surgeon. Techniques learned by the attending surgeon were immediately transferable to a new learner, who was able to achieve a faster learning curve than both the first fellow and the experienced surgeon., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Inorganic and organic constituents present in textile effluents have a noticeable effect on the performance of Fenton processes. However, studies have been focused on simple wastewater matrices that do not offer enough information to stakeholders to evaluate their real potential in large-scale facilities. Chemical auxiliaries, commonly present in textile wastewaters (NaCl = 30 g/L, Na 2 CO 3  = 5 g/L, and CH 3 COONa = 1 g/L), affect both the economic and environmental performance of the process because they increase the treatment time (from 0.5 to 24 h) and the consumption of H 2 SO 4 (657%) and NaOH (148%) during conditioning steps. The life cycle assessment (LCA) performed with the IPCC-2013 method revealed that dyeing auxiliaries increase from 1.06 to 3.73 (252%) the emissions of carbon dioxide equivalent (CO 2 -Eqv/m 3 ). Electricity consumption can be considered an environmental hotspot because it represents 60% of the carbon footprint of the Fenton process. Also, the presence of auxiliaries is critical for the process because it results in the increase of the relative impact (between 50 and 80%) in all environmental categories considered by the ReCiPe-2008 method. Chemical auxiliaries increased the costs of the treatment process in 178% (US$2.22/m 3 ) due to the higher energy consumption and the additional reagent requirements. It is worthwhile mentioning that the technical simplicity of the Fenton process and its low economic and environmental costs turn this process into an attractive alternative for the treatment of textile effluents in emerging economies.

This study evaluates the technical, economical, and environmental impact of sodium persulfate (Na 2 S 2 O 8 ) as an enhancing agent in a photo-Fenton process within a solar-pond type reactor (SPR). Photo-Fenton (PF) and photo-Fenton intensified with the addition of persulfate (PFPS) processes decolorize 97% the azo dye direct blue 71 (DB71) and allow producing a highly biodegradable effluent. Intensification with persulfate allowed reducing treatment time in 33% (from 120 to 80 min) and the consumption of chemical auxiliaries needed for pH adjustment. Energy, reagents, and chemical auxiliaries are still and environmental hotspot for PF and PFPS; however, it is worth mentioning that their environmental footprint is lower than that observed for compound parabolic concentrator (CPC)-type reactors. A life-cycle assessment (LCA) confirms that H 2 O 2 , NaOH, and energy consumption are the variables with the highest impact from an environmental standpoint. The use of persulfate reduced the relative impact in 1.2 to 12% in 12 of the 18 environmental categories studied using the ReCiPe method. The PFPS process emits 1.23 kg CO 2 (CO 2 -Eqv/m 3 treated water). On the other hand, the PF process emits 1.28 kg CO 2 (CO 2 -Eqv/m 3 treated water). Process intensification, chemometric techniques, and the use of SPRs minimize the impact of some barriers (reagent and energy consumption, technical complexity of reactors, pressure drops, dirt on the reflecting surfaces, fragility of reactor materials), limiting the application of advanced oxidation systems at an industrial level, and decrease treatment cost as well as potential environmental impacts associated with energy and reagents consumption. Treatment costs for PF processes (US$0.78/m 3 ) and PFPS processes (US$0.63/m 3 ) were 20 times lower than those reported for photo-Fenton processes in CPC-type reactors.

Non-O1, non-O139 Vibrio cholerae (NOVC) strains are an uncommon cause of gastroenteritis. However, they have been recently associated with severe extraintestinal infections in immunocompromised hosts. Among them, bacteremia in cirrhotic patients is noteworthy. We present the case of a 58-year-old woman with cirrhosis that developed septic shock, multiple organ failure and died four days after admission. Blood cultures yielded Gram-negative rods identified as Vibrio cholerae. Further serogrouping by slide agglutination and a negative PCR for ctxA gen confirmed the strain to be NOVC. Antimicrobial susceptibility testing showed sensitivity to ampicillin, chloramphenicol, tetracycline and ciprofloxacin; and resistance to trimethoprim-sulfamethoxazole. To the best of our knowledge, this is first report in Peru, described in the Hospital Nacional Dos de Mayo, of NOVC bacteremia.

Many studies about intracellular microorganisms which are important regarding diseases affecting public health have been focused on the recognition of host-pathogen interactions, thereby ascertaining the mechanisms by which the pathogen invades a cell and makes it become its host. Such knowledge enables understanding the immunological response triggered by these interactions for obtaining useful information for developing vaccines and drugs. Quantitative cell infection assay protocols are indispensable regarding studies involving Mycobacterium tuberculosis, which takes the lives of more than 2 million people worldwide every year; however, sometimes these are limited by the pathogen's slow growth. Concerning such limitation, a detailed review is presented here regarding the different methods for quantifying and differentiating an intracellular pathogen, the importance of mycobacteria aggregate dissociation and multiplicity of infection (MOI) in infection assays. The methods' differences, advantages, and disadvantages are discussed regarding intra and extracellular bacteria (on cell surface) differentiation, current problems are outlined, as are the solutions provided using fluorophores and projections made concerning quantitative infection assays., (© 2018 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.)

This article focuses on the conceptions, attitudes and practices of the inhabitants from four villages (veredas) in Tierralta and Valencia (Cordoba, Colombia), who have suffered from or are aware of the existence of cutaneous leishmaniasis. A mixed methodology was implemented based in a qualitative design using interviews and focus groups (n=45) and an epidemiological design which included applying the Montenegro test (n=251), uncovering suspected cases of cutaneous leishmaniasis in humans, (n=5) and applying epidemiological surveys (n=409). Among the results, a lack of knowledge regarding the vector was found; although respondents could identify the Lutzomyia (known as "alú"), they did not correlate it with cutaneous leishmaniasis. In addition, traditional home treatments were more frequently used, increasing the underrecording of cases. With respect to healthcare personnel, flaws in diagnosis and treatment were found, which reinforces adherence to home treatments. This scenario calls for a reflection upon the challenges of the health care system in relation to the interventions of health personnel in communities situated in endemic areas.

The emergence of multidrug-resistant Mycobacterium tuberculosis strains has led to the development of new antituberculous agents. In this context, antimicrobial targeting proteins to the cell membrane are interesting due to the avoidance of the plasma membrane permeation. Through this study, the antimicrobial activity, cellular toxicity, as well as the effect on the mycobacterial cell membrane ATPase activity of a cathelicidin-analogous peptide were assessed. By using bioinformatics analyses, a 15 amino acid LL37-analogous peptide called LLAP, which has the amino acid sequence: GRKSAKKIGKRAKRI, was designed to improve its helical structure and antibacterial activity compared to the native sequence. The LLAP peptide was synthesized, purified by RP-HPLC and its structural characteristics were determined by MALDI-TOF MS and circular dichroism. Compared to the native amino acid sequence, the minimum inhibitory concentration and cytotoxic activity of LLAP were 4.0 and 5.6-fold lower, respectively. In addition, the hemolytic activity of LLAP was lower than 1.1% and the cytotoxic activity of peptides was similar for both peptides. Interestingly, the LLAP peptide displayed approximately 50% inhibition of basal ATPase activity of the mycobacterial plasma membrane, which could in turn be associated with the impaired cell viability. The results suggest that LLAP could be considered as potential antimycobacterial compounds against cell membrane targeting ATPases. However, this antimycobacterial activity can be improved. It is expected further applications to be found for other antimicrobial peptides families based on the implemented methodology., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The TSH receptor (TSHR) extracellular domain (ECD) comprises a N-terminal leucine-rich repeat domain and an hinge region (HR), the latter contributing to ligand binding and critical for receptor activation. The crystal structure of the leucine-rich repeat domain component has been solved, but previous attempts to generate conformationally intact complete ECD or the isolated HR component for structural analysis have failed. The TSHR HR contains a C-peptide segment that is removed during spontaneous TSHR intramolecular cleavage into disulfide linked A- and B-subunits. We hypothesized that deletion of the redundant C-peptide would overcome the obstacle to generating conformationally intact TSHR ECD protein. Indeed, lacking the C-peptide region, the TSHR ECD (termed ECD-D1) and the isolated HR (termed HR-D1) were secreted into medium of insect cells infected with baculoviruses coding for these modified proteins. The identities of TSHR ECD-D1 and HR-D1 were confirmed by ELISA and immunoblotting using TSHR-specific monoclonal antibodies. The TSHR-ECD-D1 in conditioned medium was folded correctly, as demonstrated by its ability to inhibit radiolabeled TSH binding to the TSH holoreceptor. The TSHR ECD-D1 purification was accomplished in a single step using a TSHR monoclonal antibody affinity column, whereas the HR-D1 required a multistep protocol with a low yield. In conclusion, we report a novel approach to generate the TSHR ECD, as well as the isolated HR in insect cells, the former in sufficient amounts for structural studies. However, such studies will require previous complexing of the ECD with a ligand such as TSH or a thyroid-stimulating antibody.

Many intrinsically related determinants of health and disease exist, including social and economic status, education, employment, housing, and physical and environmental exposures. These factors interact to cumulatively affect health and disease burden of individuals and populations, and to establish health inequities and disparities across and within countries. Biomedical models of health care decrease adverse consequences of disease, but are not enough to effectively improve individual and population health and advance health equity. Social determinants of health are especially important in Latin American countries, which are characterised by adverse colonial legacies, tremendous social injustice, huge socioeconomic disparities, and wide health inequities. Poverty and inequality worsened substantially in the 1980s, 1990s, and early 2000s in these countries. Many Latin American countries have introduced public policies that integrate health, social, and economic actions, and have sought to develop health systems that incorporate multisectoral interventions when introducing universal health coverage to improve health and its upstream determinants. We present case studies from four Latin American countries to show the design and implementation of health programmes underpinned by intersectoral action and social participation that have reached national scale to effectively address social determinants of health, improve health outcomes, and reduce health inequities. Investment in managerial and political capacity, strong political and managerial commitment, and state programmes, not just time-limited government actions, have been crucial in underpinning the success of these policies., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The TSH receptor (TSHR) A-subunit is more effective than the holoreceptor in inducing thyroid-stimulating antibodies (TSAb) that cause Graves' disease. A puzzling phenomenon is that 2 recombinant, eukaryotic forms of A-subunits (residues 22-289), termed active and inactive, are recognized mutually exclusively by pathogenic TSAb and mouse monoclonal antibody 3BD10, respectively. Understanding the structural difference between these TSHR A-subunit forms could provide insight into Graves' disease pathogenesis. The 3-dimensional structure of the active A-subunit (in complex with a human TSAb Fab, M22) is known, but the structural difference with inactive A-subunits is unknown. We solved the 3BD10 Fab 3-dimensional crystal structure. Guided by prior knowledge of a portion of its epitope, 3BD10 docked in silico with the known active TSHR-289 monomeric structure. Because both TSAb and 3BD10 recognize the active TSHR A-subunit monomer, this form of the molecule can be excluded as the basis for the active-inactive dichotomy, suggesting, instead a role for A-subunit quaternary structure. Indeed, in silico analysis revealed that M22, but not 3BD10, bound to a TSHR-289 trimer. In contrast, 3BD10, but not M22, bound to a TSHR-289 dimer. The validity of these models is supported experimentally by the temperature-dependent balance between active and inactive TSHR-289. In summary, we provide evidence for a structural basis to explain the conformational heterogeneity of TSHR A-subunits (TSHR-289). The pathophysiologic importance of these findings is that affinity maturation of pathogenic TSAb in Graves' disease is likely to involve a trimer of the shed TSHR A-subunit.

Objective: To examine, from the point of view of a group of epidemiologists in training, their life experiences and work related to addressing mental health problems and mental health issues., Methods: An exploratory qualitative-descriptive study was conducted using ethnographic tools, non-participant observation, note-taking, and group interviews (FG)., Results: The participants mentioned that mental health and mental health issues are managed and poorly differentiated either by them and the community in general. They also said they were not ready to handle mental problems, or have the support of services for patient care, as mental health issues have not yet been clearly dimensioned by society. Epidemiology has its limitations, it focuses on knowledge of the physical-biological aspects and the use of quantitative approach with poor integration of the qualitative approach, thus hindering the understanding of a phenomenon that exceeds the limits of a research approach., Conclusions: This approach to issues of health and mental illness widens the view of knowledge from only a single focus. It includes an understanding of the qualitative approach as an option to advance the knowledge and recognition of a public health problem overshadowed by stigma and apathy of society., (Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.)

Malaria is transmitted by Plasmodium-infected anopheles mosquitoes. Widespread resistance of mosquitoes to insecticides and resistance of parasites to drugs highlight the urgent need for malaria vaccines. The most advanced malaria vaccines target sporozoites, the infective form of the parasite. A major target of the antibody response to sporozoites are the repeat epitopes of the circumsporozoite (CS) protein, which span almost one half of the protein. Antibodies to these repeats can neutralize sporozoite infectivity. Generation of protective antibody responses to the CS protein (anti-CS Ab) requires help by CD4 T cells. A CD4 T cell epitope from the CS protein designated T* was previously identified by screening T cells from volunteers immunized with irradiated P. falciparum sporozoites. The T* sequence spans twenty amino acids that contains multiple T cell epitopes restricted by various HLA alleles. Subunit malaria vaccines including T* are highly immunogenic in rodents, non-human primates and humans. In this study we characterized a highly conserved HLA-DRβ1*04:01 (DR4) restricted T cell epitope (QNT-5) located at the C-terminus of T*. We found that a peptide containing QNT-5 was able to elicit long-term anti-CS Ab responses and prime CD4 T cells in HLA-DR4 transgenic mice despite forming relatively unstable MHC-peptide complexes highly susceptible to HLA-DM editing. We attempted to improve the immunogenicity of QNT-5 by replacing the P1 anchor position with an optimal tyrosine residue. The modified peptide QNT-Y formed stable MHC-peptide complexes highly resistant to HLA-DM editing. Contrary to expectations, a linear peptide containing QNT-Y elicited almost 10-fold lower long-term antibody and IFN-γ responses compared to the linear peptide containing the wild type QNT-5 sequence. Some possibilities regarding why QNT-5 is more effective than QNT-Y in inducing long-term T cell and anti-CS Ab when used as vaccine are discussed.

Background: P-type ATPases hydrolyze ATP and release energy that is used in the transport of ions against electrochemical gradients across plasma membranes, making these proteins essential for cell viability. Currently, the distribution and function of these ion transporters in mycobacteria are poorly understood., Results: In this study, probabilistic profiles were constructed based on hidden Markov models to identify and classify P-type ATPases in the Mycobacterium tuberculosis complex (MTBC) according to the type of ion transported across the plasma membrane. Topology, hydrophobicity profiles and conserved motifs were analyzed to correlate amino acid sequences of P-type ATPases and ion transport specificity. Twelve candidate P-type ATPases annotated in the M. tuberculosis H37Rv proteome were identified in all members of the MTBC, and probabilistic profiles classified them into one of the following three groups: heavy metal cation transporters, alkaline and alkaline earth metal cation transporters, and the beta subunit of a prokaryotic potassium pump. Interestingly, counterparts of the non-catalytic beta subunits of Hydrogen/Potassium and Sodium/Potassium P-type ATPases were not found., Conclusions: The high content of heavy metal transporters found in the MTBC suggests that they could play an important role in the ability of M. tuberculosis to survive inside macrophages, where tubercle bacilli face high levels of toxic metals. Finally, the results obtained in this work provide a starting point for experimental studies that may elucidate the ion specificity of the MTBC P-type ATPases and their role in mycobacterial infections.

The TSH receptor (TSHR) hinge region, the least well understood component, bridges the leucine-rich repeat and transmembrane domains. We report data on clusters of hinge charged residues the mutation of which to Ala is compatible with cell surface expression and normal, or near normal, TSH binding affinity yet with a relative reduction in receptor activation. Mutation to Ala of E409 at the junction with the transmembrane domain was the most potent in uncoupling TSH binding and signal transduction (~22-fold less sensitive than the wild-type TSHR) and was unique among the residues studied in reducing both the amplitude and the sensitivity of the ligand-induced signal. Unexpectedly, a dual E409A/D410A mutation partially corrected the major suppressive effect of TSHR-E409A. The combined Ala substitution of a cluster of positively charged hinge residues (K287, K290, K291, R293; termed "K3R1") synergistically reduced sensitivity to TSH stimulation approximately 21-fold without altering the TSH binding affinity. Simultaneous Ala substitutions of a cluster of acidic hinge residues D392, E394, and D395 (termed "DE392-5A") partially uncoupled TSH binding from signal transduction (4.4-fold reduction in sensitivity), less than for E409A and K3R1A. Remarkably, the combination of the K3R1A and DE392-5A mutations was not additive but ameliorated the major uncoupling effect of K3R1A. This lack of additivity suggests that these two clusters contribute to a common signaling pathway. In summary, we identify several TSHR hinge residues involved in signal transmission. Our data support the concept that the hinge regions of the TSHR (and other glycoprotein hormone receptors) act as surrogate ligands for receptor activation.

The potential usefulness of antimicrobial peptides (AMPs) as antimycobacterial compounds has not been extensively explored. Although a myriad of studies on AMPs from different sources have been done, some of its mechanisms of action are still unknown. Maganins are of particular interest since they do not lyse non-dividing mammalian cells. In this work, AMPs with well-recognized activity against bacteria were synthesized, characterized, purified and their antimycobacterial activity and influence on ATPase activity in mycobacterial plasma membrane vesicles were assessed. Using bioinformatics tools, a magainin-I analog peptide (MIAP) with improved antimicrobial activity was designed. The influence of MIAP on proton (H(+)) pumping mediated by F(1)F(0)-ATPase in plasma membrane vesicles obtained from Mycobacterium tuberculosis was evaluated. We observed that the antimycobacterial activity of AMPs was low and variable. However, the activity of the designed peptide MIAP against M. tuberculosis was 2-fold higher in comparison to magainin-I. The basal ATPase activity of mycobacterial plasma membrane vesicles decreased approximately 24-30% in the presence of AMPs. On the other hand, the MIAP peptide completely abolished the F(1)F(0)-ATPase activity involved in H(+) pumping across M. tuberculosis plasma membranes vesicles at levels similar to the specific inhibitor N,N' dicyclohexylcarbodiimide. These finding suggest that AMPs can inhibit the H(+) pumping F(1)F(0)-ATPase of mycobacterial plasma membrane that potentially interferes the internal pH and viability of mycobacteria., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The TSH receptor (TSHR) comprises an extracellular leucine-rich domain (LRD) linked by a hinge region to the transmembrane domain (TMD). Insight into the orientation of these components to each other is required for understanding how ligands activate the receptor. We previously identified residue E251 at the LRD-hinge junction as contributing to coupling TSH binding with receptor activation. However, a single residue cannot stabilize the LRD-hinge unit. Therefore, based on the LRD crystal structure we selected for study four other potential LRD-hinge interface charged residues. Alanine substitutions of individual residues K244, E247, K250 and R255 (as well as previously known E251A) did not affect TSH binding or function. However, the cumulative mutation of these residues in varying permutations, primarily K250A and R255A when associated with E251A, partially uncoupled TSH binding and function. These data suggest that these three residues, spatially very close to each other at the LRD base, interact with the hinge region. Unexpectedly and most important, monoclonal antibody CS-17, a TSHR inverse agonist whose epitope straddles the LRD-hinge, was found to interact with residues K244 and E247 at the base of the convex LRD surface. These observations, together with the functional data, exclude residues K244 and E247 from the TSHR LRD-hinge interface. Further, for CS-17 accessibility to K244 and E247, the concave surface of the TSHR LRD must be tilted forwards towards the hinge region and plasma membrane. Overall, these data provide insight into the mechanism by which ligands either activate the TSHR or suppress its constitutive activity.

Introduction: Previous research has demonstrated the presence of Paragonimus spp. in crabs of three municipalities located in the Medellín river basin. To design a plan for the control and prevention of paragonimosis, parasite presence must be demonstrated in the upper area of the river, and an awareness campaign of its risks must involve the participation of the educational community in focusing attention on the local aquatic resources., Objective: The presence of Paragonimus spp. metarcercariae was established in freshwater crabs from La Miel and La Clara streams, and an awareness campaign created public awareness to management of the aquatic ecosystems for risk reduction., Materials and Methods: Nine crabs were collected from streams of La Miel and La Clara villages in 2007 and 2008. The crabs were indentified, sacrificed in the laboratory and examined for presence of Paragonimus spp. metacercariae. Five workshops were conducted with students of educational institutions of the two villages to improve the student perception of paragonimosis risks associated with the local streams., Results: The crabs were identified as Hypolobocera bouvieri. One crab was found with Paragonimus spp. in La Miel. A mollusk, Aroapyrgus colombiensis, another host of the parasite was found in La Clara. That aquatic ecosystems are a great attraction for the local was well established., Conclusions: Foci of Paragonimus spp. flatworms are present in the upper area of Medellín river which includes Caldas. However, local school children were uninformed about the risk of paragonimosis associated with the local aquatic ecosystem. Therefore this province must be included in programs for prevention and control of paragonimosis. The prevalence of this disease recommends educational programs that promote awareness of local aquatic ecosystems and their parasitic inhabitants.

Lung tissue remodeling in chronic obstructive pulmonary disease (COPD) involves diverse processes characterized by epithelial disruption, smooth muscle hypertrophy/hyperplasia, airway wall fibrosis, and alveolar destruction. According to the accepted current theory of COPD pathogenesis, tissue remodeling in COPD is predominantly a consequence of an imbalance between proteolytic and antiproteolytic activities. However, most of the studies carried out during the last few years have focused on mechanisms related to degradation of extracellular matrix (ECM) structural proteins, neglecting those involved in ECM protein deposition. This review revisits some of the latest findings related to fibrotic changes that occur in the airway wall of COPD patients, as well as the main cellular phenotypes relevant to these processes.

Background: The TlyA protein has a controversial function as a virulence factor in Mycobacterium tuberculosis (M. tuberculosis). At present, its dual activity as hemolysin and RNA methyltransferase in M. tuberculosis has been indirectly proposed based on in vitro results. There is no evidence however for TlyA relevance in the survival of tubercle bacilli inside host cells or whether both activities are functionally linked. A thorough analysis of structure prediction for this mycobacterial protein in this study shows the need for reevaluating TlyA's function in virulence., Results: Bioinformatics analysis of TlyA identified a ribosomal protein binding domain (S4 domain), located between residues 5 and 68 as well as an FtsJ-like methyltranferase domain encompassing residues 62 and 247, all of which have been previously described in translation machinery-associated proteins. Subcellular localization prediction showed that TlyA lacks a signal peptide and its hydrophobicity profile showed no evidence of transmembrane helices. These findings suggested that it may not be attached to the membrane, which is consistent with a cytoplasmic localization. Three-dimensional modeling of TlyA showed a consensus structure, having a common core formed by a six-stranded β-sheet between two α-helix layers, which is consistent with an RNA methyltransferase structure. Phylogenetic analyses showed high conservation of the tlyA gene among Mycobacterium species. Additionally, the nucleotide substitution rates suggested purifying selection during tlyA gene evolution and the absence of a common ancestor between TlyA proteins and bacterial pore-forming proteins., Conclusion: Altogether, our manual in silico curation suggested that TlyA is involved in ribosomal biogenesis and that there is a functional annotation error regarding this protein family in several microbial and plant genomes, including the M. tuberculosis genome.