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1.
Arthroscopy ; 2024 Mar 19.
Article En | MEDLINE | ID: mdl-38513877

PURPOSE: To evaluate sex-based differences in 30-day postoperative emergency department (ED) visits, 90-day complication rates, and 2-year secondary surgery rates after the Latarjet procedure for the treatment of recurrent shoulder instability. METHODS: A national administrative claims database was used to identify patients with International Classification of Diseases, Tenth Revision (ICD-10) diagnosis codes for shoulder subluxation or dislocation on the day of first-time stabilization with the Latarjet technique between 2015 and 2021. Male patients were matched 4:1 to female patients based on age, Elixhauser Comorbidity Index (ECI) score, and body mass index class. Rates of 30-day ED visits and 90-day complications were compared between cohorts, and risk factors for ED visits were identified by multivariate regression. The incidence of secondary surgery within 2 years was compared by Kaplan-Meier analysis. RESULTS: Prior to matching, 1,059 male and 360 female patients met the inclusion and exclusion criteria. Subsequent 4:1 (male-to-female) matching controlling for age, ECI score, and body mass index yielded 694 male and 185 female patients who underwent the Latarjet procedure. The overall incidence of 30-day ED visits was 9.3%, with an incidence of 8.2% for male patients and 13.5% for female patients. On the basis of multivariate logistic regression, these 30-day ED visits were associated with female sex (odds ratio, 1.79; P = .029) and incrementally higher ECI scores; relative to an ECI score of 0, ECI scores of 1 to 2, 3 to 4, and 5 or greater were associated with odds ratios of 5.31 (P = .006), 8.12 (P < .001), and 12.84 (P < .001), respectively. Ninety-day complications occurred in 1.5% of the total cohort, and the incidence was not statistically different between sexes. Overall, 2-year secondary surgery rates were similar between male and female patients (5.1% and 6.7%, respectively; P = .4). CONCLUSIONS: Female patients undergoing the Latarjet procedure for recurrent shoulder instability showed similar 90-day complication and 2-year secondary surgery rates to a matched cohort of male patients. Female sex, along with ECI score, however, was associated with a greater rate of 30-day ED visits. LEVEL OF EVIDENCE: Level III, retrospective comparative case series.

2.
Arthroscopy ; 40(4): 1279-1287, 2024 Apr.
Article En | MEDLINE | ID: mdl-37634706

PURPOSE: To review cadaveric studies evaluating the biomechanical outcomes of superior capsular reconstruction (SCR) with different graft types for the treatment of irreparable rotator cuff (RTC) tears. METHODS: PubMed, Cochrane, and Embase were queried in January 2022 to conduct this meta-analysis using the following key words: "superior capsule reconstruction," "superior capsular reconstruction," and "biomechanics." Articles were included if they reported glenohumeral superior translation or subacromial contact pressure following SCR in cadaveric RTC tears. The review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses criteria. Number of shoulders, graft types, and biomechanical outcomes were recorded and analyzed with forest plots. RESULTS: Twelve studies (95 shoulders) were included in the statistical analysis. There was a significant reduction in glenohumeral superior translation following SCR compared with RTC tear across 10 studies (79 shoulders) with standardized mean difference (SMD) -2.48 mm; confidence interval (CI) -3.28 mm, -1.69 mm. The SMD between fascia lata graft and RTC tear was -3.84 mm (CI -4.82 mm, -2.86 mm) and between dermal allograft and RTC tear was -2.05 mm (CI -3.10 mm, -1.00 mm). There was a significant reduction in subacromial contact pressure following SCR compared with RTC tear across 5 studies (55 shoulders) with SMD -3.49 MPa (CI -4.54 MPa, -2.44 MPa). The SMD between fascia lata graft and RTC tear was -3.21 MPa (CI -5.08 MPa, -1.34 MPa) and between dermal allograft and RTC tear was -3.89 MPa (CI -5.91 MPa, -1.87 MPa). CONCLUSIONS: Independent of graft type, biomechanical studies suggest that SCR improves glenohumeral superior translation and subacromial contact pressure in comparison with RTC tear at time zero. There was no definitive evidence identified in this study to suggest a biomechanically superior SCR graft option. CLINICAL RELEVANCE: Investigating the biomechanical outcomes of several graft types for superior capsular reconstruction will help surgeons better understand the efficacies of different graft types for use in superior capsule reconstruction surgery.


Rotator Cuff Injuries , Shoulder Joint , Humans , Shoulder Joint/surgery , Rotator Cuff Injuries/surgery , Shoulder , Biomechanical Phenomena , Cadaver
3.
Arthrosc Tech ; 12(10): e1737-e1745, 2023 Oct.
Article En | MEDLINE | ID: mdl-37942091

Symptomatic proximal hamstring tendon tears are typically repaired surgically, with open incision and knot-tying technique. An endoscopic, knotless, suture-bridge repair technique is presented. Potential advantages include knotless simplicity, compression over a broad zone to improve tendon-bone healing, and decreased pain secondary to elimination of knots and the open incision and approach.

4.
Hand (N Y) ; : 15589447231198267, 2023 Sep 22.
Article En | MEDLINE | ID: mdl-37737570

BACKGROUND: As racial/ethnic disparities in management of distal radius fractures (DRFs) have not been well elucidated in the literature, this study sought to evaluate the correlation of race/ethnicity on surgical versus nonsurgical management of DRFs in a Medicare population. METHODS: The PearlDiver Standard Analytical Files Medicare claims database was used to identify patients ≥65 years old with isolated DRF. Patients with polytrauma or surgery performed for upper extremity neoplasm were excluded. Surgical versus nonsurgical management was compared based on demographics, comorbidity (Elixhauser Comorbidity Index, ECI), race/ethnicity, and whether the fracture was open or closed. Univariate and multivariable analyses were used to assess for independent predictors. RESULTS: Of 54 564 isolated DRFs identified, surgery was performed for 20 663 (37.9%). On multivariable analysis, patients were independently less likely to receive surgical management if they were: older (relative to 65- to 69-year-olds, incrementally decreasing by age bracket up to >85 years where odds ratio [OR] was 0.27, P < .001), higher ECI (per 2 increase OR: 0.96, P < .001), and closed fractures (OR: 0.35, P < .001). For race/ethnicity: black (OR: 0.64, P < .001), Hispanic (OR: 0.71, P < .001), and Asian (OR: 0.60, P < .001) patients were less likely to undergo surgery. CONCLUSIONS: While age, comorbidities, and fracture type are known to affect surgical decision-making for DRF, race/ethnicity has not previously been reported, and its independent prediction of nonsurgical management for several groups points to a disparity in surgical decision-making/access to care. This highlights the need for increased attention to initiatives that seek to provide equitable care to all patients. LEVEL OF EVIDENCE: Level III-Retrospective review of national database.

5.
Cureus ; 15(5): e39635, 2023 May.
Article En | MEDLINE | ID: mdl-37388614

Acute appendicitis is one of the most common surgical emergencies worldwide. Many complications can occur secondary to complicated appendicitis including abscess formation, gangrene, sepsis, and perforation, rarely, leading to abdominal wall necrotizing fasciitis. The incidence of necrotizing fasciitis as a complication of ruptured appendicitis is extremely uncommon. The formation of an enterocutaneous fistula leading to this complication further emphasizes the rarity of such occurrence with few cases reported in the literature. Herein, we present a case of abdominal wall necrotizing fasciitis in a 72-year-old female presenting to the local emergency room with complaints of severe suprapubic abdominal pain associated with abdominal distension and acute onset foul-smelling drainage. Physical exam was significant for suprapubic and right lower quadrant abdominal tenderness with associated large indurated tender lesion and purulent weeping with large ecchymosis. Abdominal computed tomography (CT) revealed extensive subcutaneous emphysema, a large cavity with layering fluid extending into the peritoneal space, and a possible fistula formation between the intra-abdominal cavity and subcutaneous tissue. Following the diagnosis of probable necrotizing fasciitis secondary to fistula formation, the patient underwent emergent exploratory laparotomy and extensive debridement of necrotic tissue. In this report, we take the opportunity to highlight the importance of promptly recognizing and treating this uncommon complication and maintaining a high level of suspicion to prevent life-threatening consequences.

6.
Article En | MEDLINE | ID: mdl-37141180

BACKGROUND: This study evaluated the effect of race/ethnicity and socioeconomic status (SES) on surgical utilization after proximal humerus fractures in a large Medicare cohort. METHODS: The PearlDiver Medicare claims database was used to identify patients aged 65years and older with isolated, closed proximal humerus fractures, for whom race/ethnicity data were available (65.5% of identified fractures). Patients with polytrauma or neoplasm were excluded. Patient demographic, race/ethnicity, comorbidity, and median household income were compared for surgical versus nonsurgical management. Univariate and multivariable logistic regressions were used to determine disparities of surgical utilization based on the abovementioned factors. RESULTS: Of 133,218 patients with proximal humerus fracture identified, surgery was conducted for 4446 (3.3%). Those less likely to receive surgery were older (incrementally by increasing age bracket up to 85 years and older odds ratio [OR], 0.16, P < 0.001), male (OR, 0.79, P < 0.001), Black (OR, 0.51, P < 0.001) or Hispanic (0.61, P = 0.005), higher Elixhauser Comorbidity Index (per 2 increase OR, 0.86, P < 0.001), and low median household income (OR, 0.79, P < 0.001). CONCLUSIONS: The independent significance of race/ethnicity and SES point to disparities in surgical decision making/access to care. These findings highlight the need for increased attention on initiatives and policies that seek to eliminate racial disparities and improve health equity independent of SES.


Humeral Fractures , Shoulder Fractures , Humans , Male , Aged , United States/epidemiology , Ethnicity , Medicare , Socioeconomic Factors , Social Class , Shoulder Fractures/surgery
7.
Orthop J Sports Med ; 11(4): 23259671231159063, 2023 Apr.
Article En | MEDLINE | ID: mdl-37056452

Background: Arthroscopic rotator cuff repair (ARCR) is a common procedure that typically requires opioid prescription for postoperative pain management. Purpose: To investigate the current prescription patterns and factors influencing 90-day postoperative opioid prescription trends for opioid-naïve patients who underwent ARCR. Study Design: Case series; Level of evidence, 4. Methods: Opioid-naïve adult patients who underwent ARCR between January 2010 and September 2020 and had a record of opioid prescriptions during the 90-day postoperative period were identified in the PearlDiver Mariner91 national administrative database. Exclusions included patients with prior shoulder procedures, a history of chronic pain, and opioid prescription records dated earlier than 4 weeks before surgery. Covariates included age group, sex, Elixhauser Comorbidity Index, and prescriber specialty (orthopaedic or nonorthopaedic). The primary outcome-90-day postoperative morphine milligram equivalents (MMEs) prescribed per patient-was compared using univariate and multivariate regression analyses, and 90-day postoperative opioid prescription trends over the 10-year study period were analyzed with linear regression. Results: In total, 55,345 ARCR cases were identified. The mean ± SD amount prescribed within the first 90 days was 742.4 ± 256.5 MMEs, and the median was 487.5 MMEs. Multivariate linear regression analysis predicted higher 90-day postoperative MMEs for female patients and younger patients (P < .01 for both). From 2010 to 2020, there was a 66% decrease in mean MME prescribed per patient (▵ = 660.4 MME; P < .01), with a mean reduction of 55.1 MME per patient per year. In 2020, the mean 90-day postoperative amount prescribed was 341.1 MME, which is equivalent to 51 tablets of 5-mg oxycodone (Percocet). Conclusion: Female sex and younger age were predictors of more MME being prescribed after ARCR. While opioid prescriptions following ARCR have substantially decreased over the past decade, the amount prescribed warrants further attention.

8.
J Hand Surg Glob Online ; 5(2): 184-188, 2023 Mar.
Article En | MEDLINE | ID: mdl-36974296

Purpose: Increasing ownership and use of mobile phones has been recently linked to reports of hand and wrist pain from overuse, as well as more serious injuries related to distracted behaviors, such as falls and texting while driving. We describe the epidemiology of hand and wrist injuries presenting to US emergency departments from 2011 to 2020, which were associated with cell phone use using the Consumer Product Safety Commission's National Electronic Injury Surveillance System. Methods: The National Electronic Injury Surveillance System database was queried for treatment records from 2011 through to 2020 for all cell phone-related injuries of the lower arm, wrist, hand, and fingers. Using parameters provided by the National Electronic Injury Surveillance System database, there were 1,213 unique cases, yielding a total weighted estimate of 50,487 national cases presenting to emergency departments in the United States. Results: Between 2011 and 2020, the weighted estimate of annual cell phone-related injuries ranged from 3,389 to 7,320 cases. Falls were the most common cause of injury, accounting for 29.8% of estimated cases. The most common types of injuries were lacerations (22.3%). The national estimate of cell phone-related injury was the highest in the age range of 11-20 years (26.4%), followed by 21-30 years (22.2%). Women were affected more frequently than men (59.6% vs 40.4%). Conclusions: Upper extremity injuries related to cell phone use represent an increasing burden of disease to the US healthcare system. Raising awareness regarding cell phone-related injuries and in-home fall-prevention strategies, especially among elderly individuals, should be considered as means of decreasing the number of such injuries. Strategies for decreasing the burden of cell phone-related injuries occurring as a result of falls among teenagers and young adults should focus on minimizing distractions while using a cell phone. Limitations of the study include inaccuracies related to probability-weighted case estimation and limitations in reporting injuries. Clinical relevance: Knowledge of the burden of upper extremities injuries associated with this common handheld device can help to both raise awareness of this issue, as well as to potentially inform injury-prevention strategies.

9.
Spine (Phila Pa 1976) ; 48(6): 400-406, 2023 Mar 15.
Article En | MEDLINE | ID: mdl-36735637

STUDY DESIGN: A retrospective comparative cohort study. OBJECTIVE: To compare outcomes of elective non-obese anterior cervical discectomy and fusion (ACDF) patients with those that underwent bariatric surgery (BS). SUMMARY OF BACKGROUND DATA: Morbid obesity (MO) has been associated with an increased risk of complications following procedures such as elective ACDF. While pre-emptive BS has been considered for those with MO (body mass index [BMI] ≥35 kg/m 2 ), the impact of this intervention on BMI and its resultant correlation with surgical outcomes remains limited. METHODS: The PearlDiver 2010-Q1 2020 MSpine database was used to identify patients undergoing elective isolated ACDF. Three sub-cohorts were defined as follows: (1) Non-obese controls without a history of BS, (2) patients with BS procedure within two years with a BMI <35 kg/m 2 (BS+MO-), and (3) patients with BS procedure within the two years with a BMI ≥35 kg/m 2 (BS+MO+). Univariate and multivariate regression analyses were performed to compare 90-day adverse event rates adjusting for age, sex, Elixhauser Comorbidity Index, and length of stay. Kaplan-Meier analysis was performed to assess five-year cervical reoperation rates. RESULTS: Of 160,166 elective ACDF patients, prior BS was identified for 479. Of these, 136 patients were BS+MO- and 343 were BS+MO+. On multivariate analysis, BS+MO- were not at increased odds of adverse events, but BS+MO+ were at greater odds of 90-day pulmonary embolism (odds ratio 3.28, P =0.043), wound dehiscence (5.02, P <0.001), hematomas (2.52, P =0.042), and overall minor adverse events (1.61, P =0.011) compared with controls. Five-year reoperation rates were not significantly different between the groups. CONCLUSION: Twenty-eight percent of those with BS before ACDF fell out of the categorization of MO. Among this group, the odds of adverse events were similar to non-obese patients. These findings suggest that the psychological preparation and BS alone are insufficient to reduce the risk of adverse events after ACDF. Weight reduction must be achieved as well, ideally moving patients out of the BMI range for morbid obesity.


Bariatric Surgery , Obesity, Morbid , Spinal Fusion , Humans , Cohort Studies , Retrospective Studies , Spinal Fusion/methods , Obesity, Morbid/complications , Postoperative Complications/etiology , Bariatric Surgery/adverse effects , Diskectomy/adverse effects , Cervical Vertebrae/surgery
10.
J Am Acad Orthop Surg ; 31(11): 565-573, 2023 Jun 01.
Article En | MEDLINE | ID: mdl-36730692

INTRODUCTION: Bucket-handle meniscus tears are common knee injuries that are often treated surgically with meniscectomy or meniscal repair. Although clinical factors may influence the choice of one treatment approach over the other, the influence of patient, socioeconomic, and hospital factors remains poorly characterized. This study aimed to estimate the relative nationwide utilization of these two procedures and delineate a variety of factors that are associated with the selection of one treatment approach over the other. METHODS: Meniscal repair and meniscectomy procedures conducted for isolated bucket-handle meniscus tears in 2016 and 2017 were identified in the Nationwide Ambulatory Surgery Sample database. Cases were weighted using nationally representative discharge weights. Univariate analyses and a multivariable logistic regression model were used to compare patient, socioeconomic, and hospital factors associated with meniscal repair versus meniscectomy. RESULTS: In total, 12,239 cases were identified, which represented 17,236 cases after weighting. Of these, meniscal repair was conducted for 4,138 (24.0%). Based on the logistic regression model, meniscal repair was less likely for older and sicker patients. By contrast, several factors were associated with markedly higher odds of undergoing meniscal repair compared with meniscectomy. These included urban teaching hospitals; geographic location in the midwest, south, and west; and higher median household income. DISCUSSION: Using a large nationally representative cohort, the current data revealed that only 24.0% of surgically treated bucket-handle meniscus tears were treated using repair. Identification of patient, socioeconomic, and hospital factors differentially associated with meniscal repair suggest that other factors may systematically influence surgical decision-making for this patient population. Surgeons should be conscious of these potential healthcare disparities when determining the optimal treatment for their patients. LEVEL OF EVIDENCE: Level III.


Knee Injuries , Tibial Meniscus Injuries , Humans , Meniscectomy , Menisci, Tibial/surgery , Knee Injuries/surgery , Tibial Meniscus Injuries/surgery , Tibial Meniscus Injuries/complications , Hospitals, Teaching , Socioeconomic Factors , Arthroscopy/methods , Retrospective Studies
11.
JBJS Case Connect ; 12(3)2022 07 01.
Article En | MEDLINE | ID: mdl-35833648

CASE: A 43-year-old woman with dermatomyositis presented with Mycobacterium avium complex (MAC) knee septic arthritis with superimposed polymicrobial infection. After poor infection control with antibiotic therapy, she underwent debridement and antibiotic cement spacer placement, followed by knee arthrodesis 6 months later. At 2-year follow-up, she had no pain and was ambulating without assistive devices. CONCLUSION: As far as we know, this is the first reported case of MAC native-knee septic arthritis successfully treated with antibiotic cement spacer followed by knee arthrodesis. This case sheds insight on treatment strategies for a rare native-knee infection.


Arthritis, Infectious , Dermatomyositis , Mycobacterium avium-intracellulare Infection , Adult , Anti-Bacterial Agents/therapeutic use , Arthritis, Infectious/complications , Arthritis, Infectious/drug therapy , Arthritis, Infectious/surgery , Arthrodesis/adverse effects , Debridement , Dermatomyositis/complications , Female , Humans , Mycobacterium avium Complex , Mycobacterium avium-intracellulare Infection/complications , Mycobacterium avium-intracellulare Infection/drug therapy
12.
Article En | MEDLINE | ID: mdl-36733982

BACKGROUND: The associations of orthopaedic social media metrics with US News & World Report (USNWR) scores have not been well defined and are the focus of this study. METHODS: Orthopaedic surgery departments and residency programs were matched to the USNWR overall orthopaedic score and professional opinion subscore. Corresponding Instagram and Twitter accounts were evaluated for the number of followers, number following, and posts. Correlations between these metrics and rank/reputation were assessed. Pearson correlations and Student t tests were used with significance set at P < 0.05. RESULTS: Of the 192 departments associated with residency programs, there were social media accounts for 150 (78.1%) and USNWR rankings for 186 (96.9%), with an overlap of 147 (76.6%). Instagram accounts were identified for 138 (93.9%) and Twitter accounts for 85 (57.8%). Correlations were highest for the opinion subscore and number of followers (Instagram department R = 0.894, Instagram residency R = 0.338, Twitter department R = 0.808, and Twitter residency R = 0.878, P < 0.001 for each), less for the number of posts (Instagram department R = 0.590, Twitter department R = 0.521, and Twitter residency R = 0.696, P < 0.001 for each). CONCLUSION: Social media metrics correlated with USNWR scores. Focusing on such social media platforms may help further the reputation, audience engagement, and ranking of orthopaedic departments and residencies.


Internship and Residency , Orthopedics , Social Media , Humans , Hospital Departments
13.
Article En | MEDLINE | ID: mdl-36732305

INTRODUCTION: The association of preoperative narcotic use with postoperative outcomes after primary elective total knee arthroplasty (TKA) has remained poorly characterized. The NarxCare platform analyzes patients' state Prescription Drug Monitoring Program records to assign numerical scores that approximate a patient's overall opioid usage. The present study investigated the utility of admission NarxCare narcotic scores in predicting the odds of adverse events (AEs) after primary elective TKA. METHODS: Elective primary TKA patients performed at a single institution between October 2017 and May 2020 were evaluated. NarxCare narcotic scores at the time of admission, patient characteristics, 30-day AEs, readmissions, revision surgeries, and mortality were abstracted. Elective TKA patients were binned based on admission NarxCare narcotic scores. The odds of experiencing adverse outcomes were compared. RESULTS: In total, 1136 patients met the criteria for inclusion in the study (Narx Score 0: n = 293 [25.8%], 1 to 99: n = 253 [22.3%], 100 to 299: n = 368 [32.4%], 300 to 499: n = 161 [14.2%], and 500+: n = 61 [5.37%]). By logistic regression, patients with higher admission narcotic scores tended to have a dose-dependent increase in the odds of prolonged length of hospital stay, readmission within 30 days, and aggregated AEs. DISCUSSION: Admission narcotic scores may be used to predict readmission and to stratify TKA patients by risk of AEs.


Arthroplasty, Replacement, Knee , Narcotics , Humans , Length of Stay , Narcotics/adverse effects , Arthroplasty, Replacement, Knee/adverse effects , Patient Readmission , Hospitalization
14.
Biol Open ; 10(10)2021 10 15.
Article En | MEDLINE | ID: mdl-34557894

Pom152 is a transmembrane protein within the nuclear pore complex (NPC) of fungi that is important for NPC assembly and structure. Pom152 is comprised of a short amino-terminal region that remains on the cytosolic side of the nuclear envelope (NE) and interacts with NPC proteins, a transmembrane domain, and a large, glycosylated carboxy-terminal domain within the NE lumen. Here we show that the N-terminal 200 amino acids of Pom152 that include only the amino-terminal and transmembrane regions are sufficient for localization to the NPC. Full-length, glycosylation-deficient, and truncated Pom152-GFP chimeras expressed in cells containing endogenous Pom152 localize to both NPCs and cortical endoplasmic reticulum (ER). Expression of Pom152-GFP fusions in pom152Δ cells results in detectable localization at only the NE by full-length and amino-terminal Pom152-GFP fusions, but continued retention at both the NE and ER for a chimera lacking just the carboxy-terminal 377 amino acids. Neither deletion of Pom152 nor its carboxy-terminal glycosylation sites altered the nuclear protein export rate of an Msn5/Kap142 protein cargo. These data narrow the Pom152 region sufficient for NPC localization and provide evidence that alterations in other domains may impact Pom152 targeting or affinity for the NPC.


Membrane Glycoproteins/physiology , Nuclear Pore/metabolism , Protein Transport/genetics , Saccharomyces cerevisiae Proteins/physiology , Saccharomyces cerevisiae/genetics
15.
PLoS One ; 14(12): e0225806, 2019.
Article En | MEDLINE | ID: mdl-31830058

Plasmacytoid dendritic cells (PDCs) and their production of interferon-alpha (IFN-α) are believed to play an important role in human immunodeficiency virus, type I (HIV-1) pathogenesis. PDCs produce IFN-α and other proinflammatory cytokines through stimulation of Toll-like receptor 7 (TLR7) and TLR9 present in endosomal compartments. TLR7 recognizes single-stranded viral RNA, while TLR9 recognizes unmethylated DNA. In this study, we examined the mechanisms that may underlie variations in IFN-α production in response to HIV, and the impact of these variations on HIV pathogenesis. In four distinct cohorts, we examined PDC production of IFN-α upon stimulation with inactivated HIV-1 particles and unmethylated DNA. The signaling cascade of TLR7 bifurcates at the myeloid differentiation protein 88 (MyD88) adaptor protein to induce expression of either IFN-α or TNF-α. To determine whether variations in IFN-α production are modulated at the level of the receptor complex or downstream of it, we correlated production of IFN-α and TNF-α following stimulation of TLR7 or TLR9 receptors. Flow cytometry detection of intracellular cytokines showed strong, direct correlations between IFN-α and TNF-α expression in all four cohorts, suggesting that variations in IFN-α production are not due to variations downstream of the receptor complex. We then investigated the events upstream of TLR binding by using lipid-like vesicles to deliver TLR ligands directly to the TLR receptors, bypassing the need for CD4 binding and endocytosis. Similar tight correlations were found in IFN-α and TNF-α production in response to the TLR ligands. Taken together, these results strongly suggest that differences in IFN-α production depend on the regulatory processes at the level of the TLR7 receptor complex. Additionally, we found no association between IFN-α production before HIV infection and disease progression.


Adaptor Proteins, Vesicular Transport/metabolism , Dendritic Cells/metabolism , Dendritic Cells/virology , HIV-1/physiology , Interferon-alpha/biosynthesis , Toll-Like Receptor 7/metabolism , CD4-Positive T-Lymphocytes/drug effects , CD4-Positive T-Lymphocytes/metabolism , Cohort Studies , Dendritic Cells/drug effects , Disease Progression , Fatty Acids, Monounsaturated/pharmacology , Female , HIV Infections/metabolism , HIV Infections/virology , Humans , Interferon-alpha/metabolism , Male , Myeloid Differentiation Factor 88/metabolism , Quaternary Ammonium Compounds/pharmacology , Signal Transduction/drug effects , Toll-Like Receptor 7/antagonists & inhibitors , Toll-Like Receptor 9/antagonists & inhibitors , Toll-Like Receptor 9/metabolism , Tumor Necrosis Factor-alpha/biosynthesis , Viral Load/drug effects
16.
J Am Chem Soc ; 133(48): 19274-7, 2011 Dec 07.
Article En | MEDLINE | ID: mdl-22035062

Poly(diiododiacetylene) (PIDA) is a conjugated polymer containing an all-carbon backbone and only iodine atom substituents. Adding a Lewis base to the blue PIDA suspension at room temperature leads first to rapid disappearance of the absorption peaks attributed to PIDA, followed more slowly by release of free iodine. The resulting solid material gives a Raman scattering spectrum consistent with graphitic carbon, and it has a much higher conductivity than PIDA itself. Further investigation has led to the discovery of a previously unreported transformation, the reaction of a Lewis base such as pyrrolidine with a trans-diiodoalkene to form the corresponding alkyne. The generality of this iodine elimination further suggests that reaction of PIDA with Lewis bases dehalogenates the polymer, presenting a new method to prepare carbon nanomaterials at room temperature under very mild conditions.

17.
J Immunol ; 186(4): 2106-16, 2011 Feb 15.
Article En | MEDLINE | ID: mdl-21257970

Immune activation plays an important role in the pathogenesis of HIV disease. Although the causes are not fully understood, the forces that lead to immune dysfunction differ for CD4 and CD8 T cells. In this study, we report that the molecular pathways that drive immune activation during chronic HIV infection are influenced by differences in the homeostatic regulation of the CD4 and CD8 T cell pools. Proliferation of CD4 T cells is controlled more tightly by CD4 T cell numbers than is CD8 T cell proliferation. This difference reflects the importance of maintaining a polyclonal CD4 T cell pool in host surveillance. Both pools of T cells were found to be driven by viral load and its associated state of inflammation. In the setting of HIV-induced lymphopenia, naive CD4 T cells were recruited mainly into the proliferating pool in response to CD4 T cell depletion, whereas naive CD8 T cell proliferation was driven mainly by levels of HIV RNA. RNA analysis revealed increased expression of genes associated with type I IFN and common γ chain cytokine signaling in CD4 T cell subsets and only type I IFN-associated genes in CD8 T cell subsets. In vitro studies demonstrated enhanced STAT1 phosphorylation in response to IFN-α and increased expression of the IFNAR1 transcripts in naive and memory CD4 T cells compared with that observed in CD8 T cells. CD4 T cell subsets also showed enhanced STAT1 phosphorylation in response to exogenous IL-7.


CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , HIV Infections/immunology , Homeostasis/immunology , Interferon Type I/physiology , Interleukin-7/physiology , Lymphocyte Activation/immunology , RNA, Viral/physiology , Adult , CD4-CD8 Ratio , CD4-Positive T-Lymphocytes/metabolism , CD4-Positive T-Lymphocytes/virology , CD8-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/virology , Cell Proliferation , Chronic Disease , Cohort Studies , Female , HIV Infections/metabolism , HIV Infections/pathology , Humans , Interferon-alpha/physiology , Interleukin-7/pharmacology , Lymphopenia/immunology , Lymphopenia/metabolism , Lymphopenia/pathology , Male , Middle Aged , Phosphorylation/immunology , RNA, Viral/biosynthesis , RNA, Viral/blood , Resting Phase, Cell Cycle/immunology , STAT1 Transcription Factor/metabolism , Viral Load/immunology
18.
J Am Chem Soc ; 130(24): 7702-9, 2008 Jun 18.
Article En | MEDLINE | ID: mdl-18489101

Poly(diiodiacetylene), or PIDA, is a conjugated polymer containing the poly(diacetylene) (PDA) backbone but with only iodine atom substituents. The monomer diiodobutadiyne (1) can be aligned in the solid state with bis(nitrile) oxalamide hosts by hydrogen bonds between oxalamide groups and weak Lewis acid-base interactions (halogen bonds) between nitriles and iodoalkynes. The resulting cocrystals start out pale blue but turn shiny and copper-colored as the polymerization progresses. The development of a crystallization methodology that greatly improves the yield of PIDA to about 50% now allows the full characterization of the polymer by X-ray diffraction, solid-state (13)C MAS NMR, Raman, and electron absorption spectroscopy. Comparison of a series of hosts reveals an odd-even effect in the topochemical polymerization, based on the alkyl chain length of the host. In the cocrystals formed with bis(pentanenitrile) oxalamide (4) and bis(heptanenitrile) oxalamide (6), the host/guest ratio is 1:2 and the monomer polymerizes spontaneously at room temperature, while in the case of bis(butanenitrile) oxalamide (3) and bis(hexanenitrile) oxalamide (5), where the host and guest form cocrystals in a 1:1 ratio, the polymerization is disfavored and does not go to completion. The topochemical polymerization can also be observed in water suspensions of micrometer-sized 6.1 cocrystals; the size distribution of these microcrystals, and the resulting polymer chains, can be controlled by sonication. Completely polymerized PIDA cocrystals show a highly resolved vibronic progression in their UV/vis absorption spectra. Extensive rinsing of the crystals in organic solvents such as methanol, THF, and chloroform separates the polymer from the soluble host. Once isolated, PIDA forms blue suspensions in a variety of solvents. The UV/vis absorption spectra of these suspensions match the cocrystal spectrum, without the vibronic resolution. However, they also include a new longer-wavelength absorption peak, associated with aggregation of the polymer chains.


Polymers/chemical synthesis , Polymers/isolation & purification , Polyynes/chemistry , Polyynes/chemical synthesis , Polyynes/isolation & purification , Crystallization , Polyacetylene Polymer , Spectrum Analysis, Raman , X-Ray Diffraction
19.
J Am Chem Soc ; 130(13): 4415-20, 2008 Apr 02.
Article En | MEDLINE | ID: mdl-18335932

Diiodobutadiyne forms cocrystals with bis(pyridyl)oxalamides in which the diyne alignment is near the ideal parameters for topochemical polymerization to the ordered conjugated polymer, poly(diiododiacetylene) (PIDA). Nonetheless, previous efforts to induce polymerization in these samples via heat or irradiation were unsuccessful. We report here the successful ordered polymerization of diiodobutadiyne in these cocrystals, by subjecting them to high external pressure (0.3-10 GPa). At the lower end of the pressure range, the samples contain primarily monomer, as demonstrated by X-ray diffraction studies, but some polymerization does occur, leading to a pronounced color change from colorless to blue and to the development of intense Raman peaks at 962, 1394, and 2055 cm-1, corresponding to the poly(diacetylene). At higher pressures, the samples turn black and contain primarily polymer, as determined by solid-state NMR and Raman spectroscopy. Both density functional theory calculations (B3LYP/LanL2DZ) and comparisons to authentic samples of PIDA have confirmed the data analysis.

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