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BACKGROUND: Patients with gluteus medius tendinopathy present with laterally based hip pain that can be diagnosed under the greater trochanteric pain syndrome diagnosis. Magnetic resonance imaging (MRI) can assist in diagnosing pathology of the symptomatic hip, and when a pelvic MRI that includes both hips, the clinician may identify asymptomatic tears in the nonsurgical hip. In patients who undergo unilateral gluteus medius repairs, little is known about the prevalence or subsequent onset of clinical symptoms in the nonsurgical hip. PURPOSE: To describe (1) the prevalence of asymptomatic contralateral gluteus medius tears in patients with unilateral symptoms, (2) the presentation and time before symptom onset, and (3) the morphological characteristics on MRI of future symptomatic tears. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A total of 51 consecutive patients who underwent gluteus medius tear surgery were reviewed for contralateral hip pathology; of these, 43 patients were 2 years out from index surgery with reviewable preoperative MRI scans. A musculoskeletal radiologist reviewed the MRI scans for tear size, tendon retraction, and fatty infiltration using the Goutallier-Fuchs grading system. Medical record review identified contralateral hips requiring subsequent treatment. RESULTS: Of the original 43 patients, 10 (23%) had no contralateral tear, 19 (44%) had low-grade partial tears, 9 (20%) had high-grade partial tears, and 5 (11%) had full-thickness tears. Thirty-seven patients had unilateral symptoms; the other 6 had mild contralateral hip pain at enrollment. Of the 37 patients with unilateral symptoms, 27 (73%) had a contralateral tear; of those, 10 became symptomatic at an average of 24 months after index presentation (range, 6-50 months). In patients with symptomatic progression, 7 had low-grade partial tears, 1 had a high-grade partial tear, and 2 had full-thickness tears, with an average retraction of 17 mm. Tendon tear grade on MRI did not always correlate with symptoms or future presentation. All symptomatic progression remained mild to moderate. Seven patients required a corticosteroid injection, and none needed contralateral hip surgery within 2 years. CONCLUSION: Of patients who underwent surgery for a gluteus medius tear, 73% (27/37) had an incidental MRI-confirmed contralateral hip abductor tear. Of these, 37% (10/27) developed symptoms consistent with greater trochanteric pain syndrome during the 2-year study period.

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BACKGROUND: Commercially available suture anchors for rotator cuff repairs can differ significantly in architecture and material. Clinical data on their osseous integration and its effect on patient-reported outcomes is scarce. Preclinical investigations indicated a higher rate of osseous integration for the open-architecture design of the Healicoil Regenesorb anchor than the closed-threaded design of the Twinfix (Smith & Nephew). The purpose of this study was to investigate these 2 anchors with different architecture and material to determine their effect on osseous integration and clinical outcomes after rotator cuff repair. METHODS: A prospective randomized controlled trial was performed from 2014 to 2019. Sixty-four patients (39 females, 25 males) with an average age of 58.7 years who underwent arthroscopic rotator cuff repair by one of 4 board-certified, fellowship-trained surgeons were randomized to receive Healicoil Regenesorb (PLGA/ß-TCP/Calcium Sulfate) or Twinfix Ultra HA (PLLA/HA) anchors. Thirty-two patients had Healicoil anchors implanted, and 32 patients had Twinfix anchors implanted. Of the 64 patients, 51 returned at 24 months for computed tomographic (CT) examination (25 Twinfix and 26 Healicoil) to determine osteointegration of the anchors. Patient-reported outcomes, including Penn Shoulder Score (PENN), Western Ontario Rotator Cuff Index, visual analog scale, EQ-5D, Single Assessment Numeric Evaluation, Global Rating of Change, were collected at baseline, 6 weeks, 3 months, 6 months, 12 months, and 24 months. Ultrasonography was used to assess rotator cuff integrity after 6 months. Two board-certified, fellowship-trained orthopedic surgeons, blinded to the type of anchors, analyzed the CT scans to assess the anchor osteointegration at 24 months using a previously published grading scale. RESULTS: There were no differences in demographics, preoperative outcomes, or baseline characteristics such as tear size, number of anchors, Goutallier classification, or smoking status between groups. There was no difference in osseous integration between the 2 anchors at 24 months (P = .117). Eight patients had rotator cuff retears, of which 2 patients had Twinfix anchors and 6 patients had Healicoil anchors (P = .18). There were no statistically significant differences in patient-reported outcomes or complications between groups. The 2-year PENN scores were 89 with the Twinfix and 88 with Healicoil anchors (P = .55). CONCLUSION: Despite differences in material and anchor architecture, the rate of healing and patient-reported outcomes were similar between the Twinfix and Healicoil anchor groups. The rate of osteointegration was the same at 2 years.

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The development of small molecules to stabilize the G-quadruplex structure has garnered significant attention for anticancer drug discovery. Herein, we report the synthesis of several 4,4'-diaminoazobenzene derivatives containing different substituent groups and their ability to bind and stabilize telomeric G-quadruplex DNA. Circular dichroism (CD) spectroscopy was performed to characterize the quadruplex topologies, measure stabilization effects, and evaluate their capabilities for conformational photoregulation. 4,4'-Diaminoazobenzene derivatives were found to moderately stabilize quadruplex structures but not affect conformational photoregulation. This work further develops the design and general understanding of the stabilization effects of small molecules with telomeric G-quadruplex DNA.

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BACKGROUND: Civilian literature has reported excellent outcomes after elective fasciotomy for chronic exertional compartment syndrome (CECS). Our study's purpose was to objectively investigate the functional outcome of fasciotomies performed for CECS in a high demand military population. METHODS: A retrospective review of all fasciotomies performed for CECS at a single tertiary military medical center was performed. The primary outcome measure was the ability to return to full active duty. Diagnosis, operative technique, and number of compartments addressed were collected and analyzed. Patients were contacted and the visual analog scale (VAS) pain score, functional single assessment numeric evaluation (SANE) score, as well as overall satisfaction were reported. Return to duty status was collected on 70 of 70 (100%) consecutive operative extremities in 46 patients with an average follow-up of 26 months. RESULTS: Only 19 patients (41.3%) were able to return to full active duty. Ten patients (21.7%) underwent a medical separation from the military and 17 patients (37%) remained in the military but were on restricted duty secondary to persistent leg pain. Thirty-five of 46 (76%) of the patients were contacted and provided subjective feedback. The average SANE score was 72.3, and there was a mean improvement of 4.4 points in VAS score postoperatively. Overall, 71% of patients were satisfied and would undergo the procedure again. Outcomes were correlated to operative technique, patient rank, and branch of military service. CONCLUSION: Our study showed a return to full military duty in 41% of patients who underwent elective fasciotomy for CECS. Overall 78% of patients remained in the military, which is consistent with previous military literature. Subjective satisfaction rate was 71%. Both the return to activity and subjective outcomes in our study population were substantially lower than reported results in civilian populations. LEVEL OF EVIDENCE: Level IV, case series.

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Our goal was to determine whether there were age-related differences in pain, opiate use, and opiate side effects after total hip or knee arthroplasty in patients 60 years old or older. We hypothesized that there would be no significant differences between age groups in (1) mean pain score, (2) opiate use after adjusting for pain, or (3) opiate side effects after adjusting for opiate use and pain score. We retrospectively reviewed the electronic and paper charts of all patients undergoing total joint replacements at our institution over 3 years who met the following criteria: (1) 60 years old or older, (2) primary single total knee or total hip replacement, and (3) no preoperative dementia. Preoperative, intraoperative, and postoperative course data were collected using a customized data entry process and database. We divided the patients into 2 age groups, those 60 to 79 years old and those 80 years old or older. Using a marginal model with the panel variable of postoperative day, we investigated the associations between age group and pain, age group and pain adjusting for opiate use, and age group and complications (respiratory depression, naloxone usage as a measure of respiratory arrest, delirium, constipation, and urinary retention) adjusting for opiate use (Xtgee, Stata10, Stata Corp. LP, College Station, Texas). Significance was set at P < .05. We found no significant difference in pain scores between groups, but the older group had significantly fewer opiates prescribed yet significantly more side effects, including delirium (odds ratio 4.2), than did the younger group, even after adjusting for opiate dose and pain score.

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Currently, the only standardized evaluation of trauma knowledge throughout orthopedic training is found in the Orthopaedic In-Training Examination, which is administered annually to all residents by the American Academy of Orthopaedic Surgeons. Our goals were to assess the Orthopaedic In-Training Examination to (1) determine the content of the trauma questions, (2) identify the content of the 3 most frequently referenced journals on the answer keys, and (3) evaluate the correlation between those contents.We reviewed the trauma-related Orthopaedic In-Training Examination questions and answer keys for 2002 through 2007. Content for test questions and cited literature was assessed with the same criteria: (1) category type, (2) anatomic location, (3) orthopedic focus, and (4) treatment type. For each of the 3 most frequently referenced journals, we weighted content by dividing the number of times it was referenced by the number of its trauma-related articles. We then compared the journal data individually and collectively to the data from the Orthopaedic In-Training Examination trauma questions. A chi-square analysis with Yates correction was used to determine differences. Questions and literature were similar in the most frequently addressed items in each of the 4 areas: category type (taxonomy 3, treatment), 52.4% and 60.7%, respectively; anatomic location (femur), 23.3% and 27.7%, respectively; orthopedic focus (fracture), 51.0% and 56.5%, respectively; and treatment type (multiple/nonspecific), 39.0% and 35.4%, respectively.The content correlation found between the questions and literature supports the idea that reviewing current literature may help prepare for the trauma content on the Orthopaedic In-Training Examination.

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Banded garden spiders (Argiope trifasciata) were collected at the Ballona Wetlands, a metal contaminated salt marsh. The relationship between spider body size and individual metal loads was investigated. Biochemical markers were identified in spider fecal material and found to correlate to body metal levels. Body metal dry weight concentrations of Cd, Cr, Cu, Zn and total metals in female A. trifasciata exhibited distinct patterns of spatial and annual variation during 2006 and 2007. Spider body size was homogeneous across sites in both years, while increased Cd and Cr concentrations were sometimes associated with a reduction in spider size, though the influence of Cr was quite minor. Spiders with higher body Cu levels showed a reduction in peak area for hypoxanthine and an un-identified component in fecal material chromatograms. Spatial and annual differences in metal bioaccumulation are likely mediated by variation in site-specific environmental parameters and rainfall, while the negative relationships between body size and metal levels are presumably a consequence of a spider's expenditure of energy for metal tolerance mechanisms vs. foraging and growth. Finally, correlating body metal levels with excreta products constitutes a novel method to non-invasively predict metal levels in spiders.

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The properties of the self-assembly of two lipophilic guanine derivatives, 2',3',5'-O-tris(tert-butyldimethylsilyl)-guanosine and N9-(3,5-bis(tert-butyldimethylsilyloxy)-benzyl)-guanine, are described. In the presence of K+, both guanine derivatives self-associate into D4-symmetric octamers consisting of two G-quartets stacked around a central ion.

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BACKGROUND: Studies during early development have shown that the precursor availability of amino acids directly affects protein synthesis both at the whole-body level and for select organ tissues, although this has not been studied for the brain. OBJECTIVE: We utilized a mixed amino acid infusate and an insulin euglycemic clamp technique in the ovine fetus near term, with increases and decreases in circulating amino acid levels of ∼30 to 40% on average, and determined the impact on cerebral protein synthesis. METHODS: Fetal sheep received a 6-hour infusion of Primene® 10% (amino acid infusate group) or a co-infusion of insulin and 10% dextrose (insulin/dextrose infusate group) together with a continuous infusion of L-[1-(13)C]-leucine. Measurements were obtained for fetal plasma leucine enrichment at steady-state and brain tissue intracellular free and protein-bound leucine enrichment at necropsy, followed by the determination of cerebral protein fractional synthetic rates (FSR). RESULTS: Protein FSR for the cerebral cortex averaged ∼58 and ∼39%/day when using the intracellular free and plasma enrichment values for the precursor pool measurements, respectively, providing for maximal and minimal FSR values, and with little difference between the amino acid and insulin/dextrose groups, although significantly higher than respective values for the cerebellum. CONCLUSION: Accordingly, there was no evidence of a differential effect of increases versus decreases in circulating amino acids on cerebral protein synthesis as studied, which may be attributed to the saturable nature of the blood-brain barrier transporters for amino acids.

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BACKGROUND: Effective tuberculosis (TB) control in HIV-prevalent settings is hindered by absence of accurate, rapid TB diagnostic tests. We evaluated the accuracy of a urine lipoarabinomannan (LAM) test for TB diagnosis in South Africa. METHODS: Hospitalized adults with signs and/or symptoms of active TB were enrolled. Sputum smear microscopy and mycobacterial culture, mycobacterial blood culture, and HIV testing were performed. A spot urine specimen was tested for LAM. RESULTS: Four hundred ninety nine participants were enrolled; 422 (84.6%) were HIV infected. In microbiologically confirmed TB patients, the LAM test was positive in 114 of 193 [sensitivity 59%, (95% confidence interval: 52 to 66)], including 112 of 167 [67% (59 to 74)] who were HIV infected. Among individuals classified as "not TB", the LAM test was negative in 117 of 122 [specificity 96% (91 to 99)], including 83 of 88 [94% (87 to 98)] who were HIV infected. In confirmed TB patients, the LAM test was more sensitive than sputum smear microscopy (42%, 82 of 193, P < 0.001) and detected 56% (62 of 111) of those who were sputum smear negative. HIV infection [adjusted odds ratio (AOR 13.4)], mycobacteremia (AOR 3.21), and positive sputum smear (AOR 2.42) were risk factors for a positive LAM test. CONCLUSIONS: The urine LAM test detected a subset of HIV-infected patients with severe TB in whom sputum smear microscopy had suboptimal sensitivity. The combination of urine LAM testing and sputum smear microscopy is attractive for use in settings with high HIV burden.

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Amino acid infusate (Primene) and insulin euglycemic (insulin + 10% dextrose) clamp techniques were used in the ovine fetus near term and the impact on the incidence of low-voltage and high-voltage electrocortical (ECOG) activities was determined. Fetal sheep were studied over a 2-hour control period and a subsequent 6-hour experimental period.With the Primene infusion, the basic and neutral amino acids were increased by 43% and 25%, respectively, whereas the acidic amino acids showed little change. With the insulin/dextrose infusion, the basic and neutral amino acids decreased by 48% and 30%, respectively, whereas the acidic amino acids were again little changed. A small fall in arterial oxygen saturation and an increase in fetal heart rate for both groups can be attributed to an insulin-mediated increase in fetal metabolic rate. Despite the moderate increases and decreases in circulating amino acid levels, there was no significant change in the mean percent time or duration of fetal ECOG activities for either study group.

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Singlet oxygen quantum yields generated by excited state aromatic amino acids (tryptophan, tyrosine, phenylalanine), N-acetylated amino acids (N-acetyl-tryptophan, N-acetyl-tyrosine, N-acetyl-phenylalanine), and from selected proteins and immunoglobulins have been quantified by time-resolved phosphorescence measurements. A small, but significant, quantum yield found for proteins and immunoglobulins demonstrates that molecular oxygen can diffuse through the polypeptide matrix and can be sensitized by residues buried within the folds of protein structure.

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OBJECTIVE: Although the benefits of antenatal glucocorticoids are well known for infants who are born preterm, there is increasing evidence of adverse effects on brain development, which may relate to altered metabolic activity. We have determined the effect of maternal glucocorticoid administration at doses that are used clinically on cerebral substrate metabolism in the preterm ovine fetus. STUDY DESIGN: Chronically instrumented pregnant sheep at 0.85 gestation received 2 intramuscular injections of betamethasone at 170 microg/kg maternal weight (n = 13) or saline (n = 10) 24 hours apart together with a continuous infusion of L-[1-(13)C] leucine to the fetus. Fetal cerebral substrate arteriovenous differences (O2, glucose, leucine, leucine enrichment) and blood flow (fluorescent microspheres) were measured at baseline, 24 hours after the first betamethasone/saline injection (late beta/saline 1), and 4 hours after the second betamethasone/saline injection (early beta/saline 2) to obtain substrate deliveries and fractional extractions. RESULTS: Fetal pH, blood gases, and metabolites were little changed in either group over the course of the study, except for glucose values in the betamethasone animals, which increased 1.4- and 1.9-fold, measured late beta 1 and early beta 2, respectively (both P < .01). Cerebral blood flow, although little changed in the control group or at late beta 1, was decreased at early beta 2 by approximately 30% (P < .05). As such, early beta 2 animals showed a decrease in cerebral O2 delivery of approximately 20% (P = .06) and conversely an increase in cerebral glucose delivery of 1.4- and 1.3-fold at late beta 1 (P < .05) and early beta 2 (P = .08), respectively. Fractional extraction values for these substrates were not changed significantly, which resulted in corresponding decreases in estimated O2 uptake and increases in estimated glucose uptake, such that the glucose/oxygen quotient (as an index of glucose oxidative metabolism) measured 1.6 at early beta 2, which was considerably greater than baseline values at 1.1 (P < .05). Fractional extraction values for leucine and leucine enrichment averaged 2%-3%; although somewhat higher in the betamethasone animals, none of the between or within group differences were significant. CONCLUSION: Fetal cerebral metabolism in the preterm ovine fetus is altered by antenatal glucocorticoid administration, which is comparable with that used in human pregnancy, and includes an acute decrease in cerebral blood flow and a probable increase in anaerobic glucose metabolism. Although likely of short duration in conjunction with peak glucocorticoid levels, these metabolic effects may place the developing brain at added risk for superimposed hypoxic injury.

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OBJECTIVE: Although antenatal glucocorticoids have well-known benefits for infants who are born preterm by the enhancement of pulmonary maturation, adverse effects on brain growth and development have been reported in several animal-based studies. We have used the chronically catheterized ovine fetus to determine the effects of synthetic glucocorticoids that are administered at doses used clinically on cerebral protein synthesis during early brain development using [13C]-leucine tracer method. STUDY DESIGN: Chronically instrumented pregnant sheep at 0.85 gestation received 2 intramuscular injections of betamethasone at 170 microg/kg maternal weight or saline 24 hours apart together with a continuous infusion of L-[1-(13)C]-leucine to the fetus on the second day of experimentation. Measurements were obtained for fetal plasma leucine enrichment at steady-state and brain tissue intracellular free and protein-bound leucine enrichment at necropsy, followed by the determination of cerebral protein fractional synthetic rates (FSRs). A coefficient of variation was determined for plasma and tissue enrichment measurements to assess the inherent methodologic variance with the use of [13C]-leucine tracer technology. RESULTS: The cerebral protein FSR averaged approximately 112% per day and approximately 35% per day when the intracellular free and plasma enrichment values were used for the precursor pool measurements, respectively, providing for maximal and minimal FSR values. There were no differences between cortical and cerebellar tissues nor between the saline control and the betamethasone animal groups. The coefficient of variation for the plasma-enrichment values averaged approximately 2%; the coefficient of variation for the tissue enrichment values averaged approximately 10%, with an inverse relationship between the [13C]-leucine enrichment values and the coefficient of variation values. CONCLUSION: Although cerebral FSR values for the preterm ovine fetus are high and indicate high rates of protein synthesis and degradation, we found no evidence that these are altered by betamethasone as used clinically and thereby do not account for the reported structural alterations in the brain after a single-course of antenatal glucocorticoids.

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Electron transport, the proton gradient and ATP synthesis were determined in thylakoids that had been briefly exposed to a low concentration of trypsin during illumination. This treatment cleaves the gamma subunit of the ATP synthase into two large fragments that remain associated with the enzyme. Higher rates of electron transport are required to generate a given value of the proton gradient in the trypsin-treated membranes than in control membranes, indicating that the treated membranes are proton leaky. Since venturicidin restores electron transport and the proton gradient to control levels, the proton leak is through the ATP synthase. Remarkably, the synthesis of ATP by the trypsin-treated membranes at saturating light intensities is only slightly inhibited even though the proton gradient is significantly lower in the treated thylakoids. ATP synthesis and the proton gradient were determined as a function of light intensity in control and trypsin-treated thylakoids. The trypsin-treated membranes synthesized ATP at lower values of the proton gradient than the control membranes. Cleavage of the gamma subunit abrogates inhibition of the activity of the chloroplast ATP synthase by the epsilon subunit. Our results suggest that overcoming inhibition by the epsilon subunit costs energy.

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The photosensitized oxidation of 2',3',5'-tris-(O-tert-butyldimethylsilyl)-8-oxo-7,8-dihydroguanosine (8-oxoG) with singlet oxygen was studied by low-temperature NMR. A stable intermediate was characterized at -60 degrees C by (13)C, 2D NMR HMBC spectra, and chemical shifts calculated by hybrid Hartree-Fock density functional theory which agreed with the structure 5-hydroperoxy-8-oxo-7,8-dihydroguanosine. Reduction of this intermediate at low temperature afforded the corresponding alcohol, the long-postulated 5-hydroxy-8-oxo-7,8-dihydroguanosine, the last intermediate in the formation of spiroiminodihydantoin. Upon warming to room temperature, this alcohol rearranges to form the spiroiminodihydantoin in good yield within 2 h.

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