Structure, mechanism, and inhibition of Hedgehog acyltransferase.

The Sonic Hedgehog (SHH) morphogen pathway is fundamental for embryonic development and stem cell maintenance and is implicated in various cancers. A key step in signaling is transfer of a palmitate group to the SHH N terminus, catalyzed by the multi-pass transmembrane enzyme Hedgehog acyltransferase (HHAT). We present the high-resolution cryo-EM structure of HHAT bound to substrate analog palmityl-coenzyme A and a SHH-mimetic megabody, revealing a heme group bound to HHAT that is essential for HHAT function. A structure of HHAT bound to potent small-molecule inhibitor IMP-1575 revealed conformational changes in the active site that occlude substrate binding. Our multidisciplinary analysis provides a detailed view of the mechanism by which HHAT adapts the membrane environment to transfer an acyl chain across the endoplasmic reticulum membrane. This structure of a membrane-bound O-acyltransferase (MBOAT) superfamily member provides a blueprint for other protein-substrate MBOATs and a template for future drug discovery.

Association of Atrial Fibrillation Burden and Mortality Among Patients With Cardiac Implantable Electronic Devices.

BACKGROUND: Current estimates of atrial fibrillation (AF)-associated mortality rely on claims- or clinical-derived diagnoses of AF, limit AF to a binary entity, or are confounded by comorbidities. The objective of the present study is to assess the association between device-recognized AF and mortality among patients with cardiac implantable electronic devices capable of sensitive and continuous atrial arrhythmia detection. Secondary outcomes include relative mortality among cohorts with no AF, paroxysmal AF, persistent AF, and permanent AF. METHODS: Using the deidentified Optum Clinformatics US claims database (2015 to 2020) linked to the Medtronic CareLink database, we identified individuals with a cardiac implantable electronic device who transmitted data ≥6 months after implantation. AF burden was assessed during the first 6 months after implantation (baseline period). Subsequent mortality, assessed from claims data, was compared between patients with and without AF, with adjustment for age, geographic region, insurance type, Charlson Comorbidity Index, and implantation year. RESULTS: Of 21 391 patients (age, 72.9±10.9 years; 56.3% male) analyzed, 7798 (36.5%) had device-recognized AF. During a mean of 22.4±12.9 months (median, 20.1 [12.8-29.7] months) of follow-up, the overall incidence of mortality was 13.5%. Patients with AF had higher adjusted all-cause mortality than patients without AF (hazard ratio, 1.29 [95% CI, 1.20-1.39]; P<0.001). Among those with AF, patients with nonparoxysmal AF had the greatest risk of mortality (persistent AF versus paroxysmal AF: hazard ratio, 1.36 [95% CI, 1.18-1.58]; P<.001; permanent AF versus paroxysmal AF: hazard ratio, 1.23 [95% CI, 1.14-1.34]; P<.001). CONCLUSIONS: After adjustment for potential confounding factors, the presence of AF was associated with higher mortality in our cohort of patients with cardiac implantable electronic devices. Among those with AF, nonparoxysmal AF was associated with the greatest risk of mortality.

Impact of nocturnal hypoxia on glycaemic control, appetite, gut microbiota and inflammation in adults with type 2 diabetes mellitus: A single-blind cross-over trial.

High altitude residents have a lower incidence of type 2 diabetes mellitus (T2DM). Therefore, we examined the effect of repeated overnight normobaric hypoxic exposure on glycaemic control, appetite, gut microbiota and inflammation in adults with T2DM. Thirteen adults with T2DM [glycated haemoglobin (HbA1c): 61.1 ± 14.1 mmol mol-1; aged 64.2 ± 9.4 years; four female] completed a single-blind, randomised, sham-controlled, cross-over study for 10 nights, sleeping when exposed to hypoxia (fractional inspired O2 [ F I O 2 ${{F}_{{\mathrm{I}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$ ] = 0.155; ∼2500 m simulated altitude) or normoxic conditions ( F I O 2 ${{F}_{{\mathrm{I}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$  = 0.209) in a randomised order. Outcome measures included: fasted plasma [glucose]; [hypoxia inducible factor-1α]; [interleukin-6]; [tumour necrosis factor-α]; [interleukin-10]; [heat shock protein 70]; [butyric acid]; peak plasma [glucose] and insulin sensitivity following a 2 h oral glucose tolerance test; body composition; appetite indices ([leptin], [acyl ghrelin], [peptide YY], [glucagon-like peptide-1]); and gut microbiota diversity and abundance [16S rRNA amplicon sequencing]. During intervention periods, accelerometers measured physical activity, sleep duration and efficiency, whereas continuous glucose monitors were used to assess estimated HbA1c and glucose management indicator and time in target range. Overnight hypoxia was not associated with changes in any outcome measure (P > 0.05 with small effect sizes) except fasting insulin sensitivity and gut microbiota alpha diversity, which exhibited trends (P = 0.10; P = 0.08 respectively) for a medium beneficial effect (d = 0.49; d = 0.59 respectively). Ten nights of overnight moderate hypoxic exposure did not significantly affect glycaemic control, gut microbiome, appetite, or inflammation in adults with T2DM. However, the intervention was well tolerated and a medium effect-size for improved insulin sensitivity and reduced alpha diversity warrants further investigation. KEY POINTS: Living at altitude lowers the incidence of type 2 diabetes mellitus (T2DM). Animal studies suggest that exposure to hypoxia may lead to weight loss and suppressed appetite. In a single-blind, randomised sham-controlled, cross-over trial, we assessed the effects of 10 nights of hypoxia (fractional inspired O2 ∼0.155) on glucose homeostasis, appetite, gut microbiota, inflammatory stress ([interleukin-6]; [tumour necrosis factor-α]; [interleukin-10]) and hypoxic stress ([hypoxia inducible factor 1α]; heat shock protein 70]) in 13 adults with T2DM. Appetite and inflammatory markers were unchanged following hypoxic exposure, but an increased insulin sensitivity and reduced gut microbiota alpha diversity were associated with a medium effect-size and statistical trends, which warrant further investigation using a definitive large randomised controlled trial. Hypoxic exposure may represent a viable therapeutic intervention in people with T2DM and particularly those unable or unwilling to exercise because barriers to uptake and adherence may be lower than for other lifestyle interventions (e.g. diet and exercise).

An Approach to Recurrent Clubfoot Deformity in Adolescents.

Even under ideal circumstances, recurrence of infantile clubfoot deformity following the Ponseti method of treatment is to be expected to occur in as many as 20% of patients. When encountered early in childhood, these recurrences are usually amenable to further casting and limited surgery. Creation of a plantigrade foot, however, becomes much more challenging when recurrences present during adolescence and early adulthood. Because of the stiffer nature of these deformities in older patients, the fact that they are often more severe because of varying lengths of neglect, and the often deleterious effects of prior intra-articular surgeries on joint health, a principled approach is recommended for both the assessment of these feet and development of an appropriate treatment plan. In doing so, the surgeon can select the combination of nonsurgical and surgical interventions that allows for as little surgery as possible to create a plantigrade foot while maintaining any motion that is present before treatment. Although no single algorithmic approach can be applied to the variety of deformities and potentially complicating factors that are encountered in treating such patients, an understanding of the utility of preoperative casting, gradual and acute corrective techniques, and the importance of identifying and mitigating deforming forces and tendon imbalance can greatly optimize outcomes.

Metaphyseal Fracture Displacement is Predictive of Intra-articular Diastasis in Adolescent Triplane Ankle Fractures.

BACKGROUND: Triplane fractures are rare enough that large homogeneous series to support management decisions are lacking. During initial evaluation, the addition of computed tomography (CT) to conventional X-rays (XR) does not always alter the patient's clinical course. Therefore, routine use of CT is controversial. This study aims to: (1) clarify quantitative relationships between articular displacement measured on XR versus CT and (2) identify whether metaphyseal displacement on the lateral XR predicts clinically relevant articular displacement on a CT scan. METHODS: A 10-year retrospective review of consecutive triplane fractures was performed at a level 1 pediatric trauma center. Maximum articular and metaphyseal displacement were recorded from XR and CT. Quantitative relationships between XR and CT measurements were compared among imaging modalities and radiographically operative versus nonoperative fractures. RESULTS: Eighty-seven patients met the inclusion criteria. XR underestimated articular displacement by 229% in the sagittal plane (1 mm on XR vs 3.3 mm on CT; P < 0.05) and 17% in the coronal plane (2.3 mm on XR vs 2.7 mm on CT; P < 0.05). XR underestimated articular step-off by 184% in the coronal plane and 177% in the sagittal plane ( P < 0.05). CT measurements more often differentiated patients who did or did not undergo surgery at our institution. Metaphyseal displacement was significantly higher in patients with traditionally operative articular displacement (≥2.5 mm on CT) versus those with articular displacement below traditionally operative thresholds (2.4 vs 0.9 mm, P = 0.001). Sixty patients had metaphyseal displacement >1 mm on the lateral XR, of whom 56 had surgical-magnitude articular displacement (≥2.5 mm) on CT (positive predictive value = 94%). CONCLUSIONS: Conventional radiographs underestimate the true articular displacement of triplane fractures. Surgical-magnitude articular step-off is rare, and the largest articular gap is usually visualized on the axial CT image. Metaphyseal displacement >1 mm, which is easily measured on a lateral XR, is strongly predictive of clinically relevant articular displacement on CT. This radiographic finding should prompt advanced imaging before proceeding with nonoperative management. LEVEL OF EVIDENCE: Level III.

Obesity Increases Risk for Wound Complications After Pediatric Foot Surgery: A Retrospective Cohort Review Using the NSQIP-Pediatric Database.

BACKGROUND: As the incidence of childhood obesity continues to rise, so too does the number of obese children who undergo foot surgery. As the childhood obesity epidemic rolls on, pediatric orthopaedic surgeons will encounter obese patients with even greater frequency. Therefore, a comprehensive understanding of the risks associated with obesity is valuable to maximize patient safety. The purpose of this study is to retrospectively evaluate the relationship between obesity and postoperative outcomes in patients undergoing pediatric foot surgery across multiple institutions using a large national database. METHODS: Pediatric patients who had undergone foot surgery were retrospectively identified using the American College of Surgeons 2012-2017 Pediatric National Surgical Quality Improvement (ACS-NSQIP-Pediatric) database by cross-referencing reconstructive foot-specific CPT codes with ICD-9/ICD-10 diagnosis codes. Center for Disease Control BMI-to-age growth charts were used to stratify patients into normal-weight and obese cohorts. Univariate and multivariate analyses were performed to describe and assess outcomes in obese compared with normal-weight patients. RESULTS: Of the 3924 patients identified, 1063 (27.1%) were obese. Compared with normal-weight patients, obese patients were more often male (64.7% vs. 58.7%; P =0.001) and taller (56.3 vs. 51.3 inches; P <0.001). Obese patients had significantly higher rates of overall postoperative complications (3.01% vs. 1.32%; P =0.001) and wound dehiscence (1.41% vs. 0.59%; P =0.039). Multivariate analysis found that obesity was an independent predictor of both wound dehiscence [adjusted odds ratio (OR)=2.16; 95% CI=1.05-4.50; P =0.037] and surgical site infection (adjusted OR=3.03; 95% CI=1.39-6.61; P =0.005). Subgroup analysis of patients undergoing clubfoot capsular release procedures identified that obese patients had a higher rate of wound dehiscence (3.39% vs. 0.51%; P =0.039) compared with normal-weight patients. In multivariate analysis, obesity was an independent predictor of dehiscence (adjusted OR=5.71; 95% CI=1.46-22.31; P =0.012) in this procedure group. There were no differences in complication rates between obese and normal-weight patients in a subgroup analysis of tarsal coalition procedures or clubfoot tibialis anterior tendon transfer procedures. CONCLUSION: Obese children undergoing foot surgery had higher overall complication rates, wound complications, and surgical site infections compared with children of normal weight. As the incidence of childhood obesity continues to rise, this information may be useful in assessing and discussing surgical risks with patients and their families. LEVEL OF EVIDENCE: III.

Effect of Body Mass Index on Pedobarographic and Patient-Reported Outcome Measures in Adolescent Flexible Flat Feet.

BACKGROUND: Although adolescent flexible flatfoot deformity (FFD) is common, little is known regarding the effect of weight on associated symptomatology. This study uses pedobarography and patient-reported outcome measures (PROs) to determine if overweight adolescents with FFD have more severe alterations in dynamic plantar pressures than normal body mass index percentiles (wnBMI) with FFD and if such alterations correlate with pain and activity. METHODS: A retrospective review of patients aged 10 to 18 years with nonsyndromic symptomatic FFD was performed. Overweight (BMI percentile ≥ 85%) patients were compared with wnBMI patients with regard to dynamic plantar pressure measures and PRO scores. Pedobarographic data were subdivided into regions: medial/lateral hindfoot and midfoot, and first, second, and third to fifth metatarsals. Plantar pressure variables were normalized to account for differences in foot size, body weight, and walking speed. Contact area (CA%), maximum force by body weight (MF%), and contact time as a percentage of the rollover process (CT%) were calculated. Two foot-specific PROs were assessed, including the Foot and Ankle Outcome Score and the Oxford Ankle Foot Measure for Children. RESULTS: Of the 48 adolescents studied, 27 (56%) were overweight and 21 (44%) were wnBMI. After normalization of the data, overweight patients had significantly greater medial midfoot MF%, whereas CT% was increased across the medial and lateral midfoot and hindfoot regions. Correlations showed positive trends: as BMI percentile increases, so will CA and MF in the medial midfoot, as well as CT in the medial and lateral midfoot and hindfoot. Significant differences were seen between groups, with the overweight group reporting lower sports and recreation subscores than the wnBMI group. No significant differences were seen in the pain and disability subscores. CONCLUSIONS: Although overweight adolescents with FFD exhibit greater forces and more time spent during the rollover process in the medial midfoot than normal-weight patients, they did not report worse pain or disability associated with their flat foot deformity. LEVEL OF EVIDENCE: Therapeutic level 3.

Inappropriate Pediatric Orthopaedic Emergency Department Transfers: A Burden on the Health Care System.

BACKGROUND: Though the importance of level 1 pediatric trauma has repeatedly been shown to lessen both morbidity and mortality in critically injured children, these same tertiary referral centers also receive numerous transfers of patients with less severe injuries. This not only leads to increased costs and use of limited facility resources but, oftentimes, frustration and unnecessary expense to those families for whom transfer was avoidable. Prior work has demonstrated that half of all inappropriate pediatric interfacility transfers are due to orthopedic injuries. This study aims to evaluate the incidence of inappropriate transfers of pediatric patients with isolated orthopedic injuries to a pediatric level 1 trauma center and identify factors associated with such transfers. METHODS: All patients transferred to a large metropolitan level 1 pediatric trauma center for isolated orthopedic injuries over a 6-year period were retrospectively evaluated. Medical records were reviewed for demographic and injury data, including age, gender, race, social deprivation index, insurance status, location of transferring institution, timing of transfer, and availability of orthopedic on-call coverage at transferring institution. The transfer was deemed to be appropriate if the patient required a sedated reduction, was admitted to the hospital, or was taken to the operating room within 24 hours of transfer. Regression analysis was reviewed for each of the demographic, patient, and transfer characteristics in an attempt to isolate those associated with inappropriate transfer. RESULTS: In all, 437 transfers occurred during the study period. Of these, 112 (26%) were deemed inappropriate. 4% of patients transferred for orthopedic injuries did not receive an orthopedic consult following the transfer. Non-white patients were more likely than white patients to be transferred inappropriately (34.01% vs. 21.58%, P=0.009 ). No other demographic characteristic was predictive of inappropriate transfer. There was no difference in the rate of appropriate transfer between patients with private insurance versus government-funded, self-paying, or uninsured patients. The timing of transfer (night vs. day and weekday vs. weekend) did not affect the appropriateness of transfer. Facilities with orthopaedic on-call coverage were more likely to inappropriately transfer patients than those without (26.6% vs. 23.4%, P<0.001 ). CONCLUSION: A quarter of patients transferred for isolated orthopaedic injuries were inappropriately transferred. Unlike studies published in adult literature, the timing of transfer (overnight and weekend) and the insurance status of the patient did not appear to play a role in the appropriateness of transfer. Inappropriate and unnecessary trauma transfers create a significant burden on tertiary referral centers. Raising awareness of the high incidence of unnecessary transfers coupled with enhanced education of outside emergency medicine providers may result in better stewardship of health care resources, limit delays in patient care, and reduce strain on both the health care delivery system and the families of injured children. LEVEL OF EVIDENCE: Level III-Therapeutic Study.

The effect of repeated hot water immersion on insulin sensitivity, heat shock protein 70, and inflammation in individuals with type 2 diabetes mellitus.

Repeated hot water immersion (HWI) can improve glycemic control in healthy individuals but data are limited for individuals with type 2 diabetes mellitus (T2DM). The present study investigated whether repeated HWI improves insulin sensitivity and inflammatory status and reduces plasma ([extracellular heat shock protein 70]) [eHSP70] and resting metabolic rate (RMR). Fourteen individuals with T2DM participated in this pre- versus postintervention study, with outcome measures assessed in fasted (≥12 h) and postprandial (2-h post-75 g glucose ingestion) states. HWI consisted of 1 h in 40°C water (target rectal temperature 38.5°C-39°C) repeated 8-10 times within a 14-day period. Outcome measures included insulin sensitivity, plasma [glucose], [insulin], [eHSP70], inflammatory markers, RMR, and substrate utilization. The HWI intervention increased fasted insulin sensitivity (QUICKI; P = 0.03) and lowered fasted plasma [insulin] (P = 0.04), but fasting plasma [glucose] (P = 0.83), [eHSP70] (P = 0.08), [IL-6] (P = 0.55), [IL-10] (P = 0.59), postprandial insulin sensitivity (P = 0.19), plasma [glucose] (P = 0.40), and [insulin] (P = 0.47) were not different. RMR was reduced by 6.63% (P < 0.05), although carbohydrate (P = 0.43) and fat oxidation (P = 0.99) rates were unchanged. This study shows that 8-10 HWIs within a 14-day period improved fasting insulin sensitivity and plasma [insulin] in individuals with T2DM, but not when glucose tolerance is challenged. HWI also improves metabolic efficiency (i.e., reduced RMR). Together these results could be clinically important and have implications for metabolic health outcomes and well-being in individuals with T2DM.NEW & NOTEWORTHY This is the first study to investigate repeated HWI to raise deep body temperature on insulin sensitivity, inflammation, eHSP70, and substrate utilization in individuals with T2DM. The principal novel findings were improvements in fasting insulin sensitivity and fasting plasma [insulin] but no change in fasting plasma [glucose], postprandial insulin sensitivity, plasma [insulin], or [glucose]. There was also no change in eHSP70, inflammatory status, or substrate utilization but there were reductions in RMR and oxygen consumption.

Occurrence of virulence determinants in vibrio cholerae, vibrio mimicus, vibrio alginolyticus, and vibrio parahaemolyticus isolates from important water resources of Eastern Cape, South Africa.

BACKGROUND: Virulence determinants are crucial to the risk assessment of pathogens in an environment. This study investigated the presence of eleven key virulence-associated genes in Vibrio cholerae (n = 111) and Vibrio mimicus (n = 22) and eight virulence determinants in Vibrio alginolyticus (n = 65) and Vibrio parahaemolyticus (n = 17) isolated from six important water resources in Eastern Cape, South Africa, using PCR techniques. The multiple virulence gene indexes (MVGI) for sampling sites and isolates as well as hotspots for potential vibriosis outbreaks among sampling sites were determined statistically based on the comparison of MVGI. RESULT: The PCR assay showed that all the V. cholerae isolates belong to non-O1/non-O139 serogroups. Of the isolates, Vibrio Cholera (84%), V. mimicus (73%), V. alginolyticus (91%) and V. parahaemolyticus (100%) isolates harboured at least one of the virulence-associated genes investigated. The virulence gene combinations detected in isolates varied at sampling site and across sites. Typical virulence-associated determinants of V. cholerae were detected in V. mimicus while that of V. parahaemolyticus were detected in V. alginolyticus. The isolates with the highest MVGI were recovered from three estuaries (Sunday river, Swartkopps river, buffalo river) and a freshwater resource (Lashinton river). The cumulative MVGI for V. cholerae, V. mimicus, V. alginolyticus and V. parahaemolyticus isolates were 0.34, 0.20, 0.45, and 0.40 respectively. The targeted Vibrio spp. in increasing order of the public health risk posed in our study areas based on the MVGI is V. alginolyticus > V. parahaemolyticus > V. cholerae > V. mimicus. Five (sites SR, PA5, PA6, EL4 and EL6) out of the seventeen sampling sites were detected as the hotspots for potential cholera-like infection and vibriosis outbreaks. CONCLUSIONS: Our findings suggest that humans having contact with water resources in our study areas are exposed to potential public health risks owing to the detection of virulent determinants in human pathogenic Vibrio spp. recovered from the water resources. The study affirms the relevancy of environmental Vibrio species to the epidemiology of vibriosis, cholera and cholera-like infections. Hence we suggest a monitoring program for human pathogenic Vibrio spp. in the environment most especially surface water that humans have contact with regularly.

Plasma biomarkers of endothelial function, inflammation and oxidative stress in individuals with non-freezing cold injury.

NEW FINDINGS: What is the central question of this study? Are biomarkers of endothelial function, oxidative stress and inflammation altered by non-freezing cold injury (NFCI)? What is the main finding and its importance? Baseline plasma [interleukin-10] and [syndecan-1] were elevated in individuals with NFCI and cold-exposed control participants. Increased [endothelin-1] following thermal challenges might explain, in part, the increased pain/discomfort experienced with NFCI. Mild to moderate chronic NFCI does not appear to be associated with either oxidative stress or a pro-inflammatory state. Baseline [interleukin-10] and [syndecan-1] and post-heating [endothelin-1] are the most promising candidates for diagnosis of NFCI. ABSTRACT: Plasma biomarkers of inflammation, oxidative stress, endothelial function and damage were examined in 16 individuals with chronic NFCI (NFCI) and matched control participants with (COLD, n = 17) or without (CON, n = 14) previous cold exposure. Venous blood samples were collected at baseline to assess plasma biomarkers of endothelial function (nitrate, nitrite and endothelin-1), inflammation [interleukin-6 (IL-6), interleukin-10 (IL-10), tumour necrosis factor alpha and E-selectin], oxidative stress [protein carbonyl, 4-hydroxy-2-nonenal (4-HNE), superoxide dismutase and nitrotyrosine) and endothelial damage [von Willebrand factor, syndecan-1 and tissue type plasminogen activator (TTPA)]. Immediately after whole-body heating and separately, foot cooling, blood samples were taken for measurement of plasma [nitrate], [nitrite], [endothelin-1], [IL-6], [4-HNE] and [TTPA]. At baseline, [IL-10] and [syndecan-1] were increased in NFCI (P < 0.001 and P = 0.015, respectively) and COLD (P = 0.033 and P = 0.030, respectively) compared with CON participants. The [4-HNE] was elevated in CON compared with both NFCI (P = 0.002) and COLD (P < 0.001). [Endothelin-1] was elevated in NFCI compared with COLD (P < 0.001) post-heating. The [4-HNE] was lower in NFCI compared with CON post-heating (P = 0.032) and lower than both COLD (P = 0.02) and CON (P = 0.015) post-cooling. No between-group differences were seen for the other biomarkers. Mild to moderate chronic NFCI does not appear to be associated with a pro-inflammatory state or oxidative stress. Baseline [IL-10] and [syndecan-1] and post-heating [endothelin-1] are the most promising candidates for diagnosing NFCI, but it is likely that a combination of tests will be required.

Multi-gene phylogeny of North American clear-winged moths (Lepidoptera: Sesiidae): a foundation for future evolutionary study of a speciose mimicry complex.

Sesiids are a diverse group of predominantly diurnal moths, many of which are Batesian mimics of Hymenoptera. However, their diversity and relationships are poorly understood. A multi-gene phylogenetic analysis of 48 North American sesiid species confirmed the traditional taxonomic tribal ranks, demonstrated the paraphyly of Carmenta and Synanthedon with respect to several other genera and ultimately provided minimal phylogenetic resolution within and between North American and European groups. Character support from each gene suggested inconsistency between the phylogenetic signal of the CAD gene and that of the other four genes. However, removal of CAD from subsequent phylogenetic analyses did not substantially change the initial phylogenetic results or return Carmenta and Synanthedon as reciprocally monophyletic, suggesting that it was not impacting the overall phylogenetic signal. The lack of resolution using genes that are typically informative at the species level for other lepidopterans suggests a surprisingly rapid radiation of species in Carmenta/Synanthedon. This group also exhibits a wide range of mimicry strategies and hostplant usage, which could be fertile ground for future study.

Gold and Silver Chains from Tetrahydrothiophenocucurbit[6]uril as Au or Ag-Nanoparticles.

Tetrahydrothiophenocucurbit[5 and 6]uril has been synthesized from tetrathiophenoglycoluril diether, providing thioether functionality at the exterior equatorial position of the cucurbituril cage. This functionality has been investigated for chemical modification through sulfoxide formation and subsequent Pummerer rearrangement to the acetoxy derivative of the tetrahydrothiophenocucurbit[5]uril. Nanoparticles of Au and Ag were prepared in the presence of tetrahydrothiophenocucurbit[6]uril, which curiously led to the formation of nanoparticle chains, growing in length over days to weeks.

Virulence Signatures, Integrons, and Antibiotic Resistance Genes in Bacterial Strains Recovered from Selected Commercial Dairy Products and Fresh Raw Meat.

Bacterial species responsible for food infections and intoxication are sometimes carried through the food production and processing. Very few published literatures exist on integrons among antibiotic-resistant staphylococcal strains from foods of animal origin in Gauteng Province, South Africa, hence this study. A total of 720 samples (360 meat and 360 dairies) from a community abattoir of a research farm in South Africa, using conventional bacteriological and molecular methods. Nine (9) bacterial strains, including Bacillus subtilis AYO-123, Acinetobacter baumannii AYO-241, Staphylococcus lentus AYO-352, among others were identified and submitted to GenBank. More bacterial strains were recovered from raw meat (90.5%) than dairy products (9.5%). Resistance was shown (0-100%) to Imipenem, Meropenem, Norfloxacin, Clindamycin, and 22 other antibiotics, without any carbapenem-resistant Acinetobacter baumannii and methicillin/vancomycin-resistant Staphylococcus species (MRSS/VRSS). Virulence genes for fibronectin-binding protein A (FnbA) were predominant (56.24%) followed by the circulating nucleic acids (cna) gene (43.75%). Others were staphylococcal enterotoxin A (sea, 41%), staphylococcal enterotoxin B (seb, 23.5%). Co-presence of sea and seb genes occurred in 11.76% of the isolates, but no coa genes was amplified. Antibiotic resistance genes (ARGs), tetK (70.58%), linA (29.4%), and ermA (11.76%) were detected, but none of the mecA and vat genes was amplified. Class 2 integron (50%) was more predominantly detected than integron 1 (25%), but no Class 3 integron was detected. Bacteria with both the detected virulence and antibiotic resistance genes are of potential risks to human health.

The Ponseti Method for the Treatment of Clubfeet Associated With Down Syndrome: A Single-institution 18-year Experience.

BACKGROUND: Although the Ponseti method has been used with great success in a variety of nonidiopathic clubfoot deformities, the efficacy of this treatment in clubfeet associated with Down syndrome remains unreported. The purpose of this study is, therefore, to compare treatment characteristics and outcomes of clubfoot patients with Down syndrome to those with idiopathic clubfoot treated with the Ponseti method. METHODS: An Institutional Review Board-approved, retrospective review of prospectively gathered data were performed at a single pediatric hospital over an 18-year period. Patients with either idiopathic clubfeet or clubfeet associated with Down syndrome who were less than 1 year of age at the outset of treatment were treated by the Ponseti method, and had a minimum of 2 year's follow-up were included. Initial Dimeglio score, number of casts, need for heel cord tenotomy, recurrence, and need for further surgery were recorded. Outcomes were classified using the Richards classification system: "good" (plantigrade foot +/- heel cord tenotomy), "fair" (need for a limited procedure), or "poor" (need for a full posteromedial release). RESULTS: Twenty clubfeet in 13 patients with Down syndrome and 320 idiopathic clubfeet in 215 patients were identified. Average follow-up was 73 months for the Down syndrome cohort and 62 months for the idiopathic cohort. Down syndrome patients presented for treatment at a significantly older age (61 vs. 16 d, P =0.00) and with significantly lower average initial Dimeglio scores than the idiopathic cohort (11.3 vs. 13.4, P =0.02). Heel cord tenotomy was performed in 80% of the Down syndrome cohort and 79% of the idiopathic cohort ( P =1.00). Recurrence rates were higher in the Down syndrome cohort (60%) compared with the idiopathic group (37%), but this difference was not statistically significant ( P =0.06). Need for later surgical procedures was similar between the 2 cohorts, though recurrences in the Down syndrome group were significantly less likely to require intra-articular surgery (8.3% vs. 65.5%, P =0.00). Clinical outcomes were 95% "good," 0% "fair," and 5% "poor" in the Down syndrome cohort and 69% "good," 27% "fair," and 4% "poor" in the idiopathic cohort ( P =0.01). CONCLUSIONS: Despite the milder deformity and an older age at presentation, clubfeet associated with Down syndrome have similar rates of recurrence and may have better clinical outcomes when compared with their idiopathic counterparts. When deformities do relapse in Down syndrome patients, significantly less intra-articular surgery is required than for idiopathic clubfeet. LEVEL OF EVIDENCE: Level III.

Reconceptualizing the Juvenile Bunion.

BACKGROUND: The operative management of the juvenile bunion has not enjoyed the same level of success as its adult counterpart leading to the concern that we do not fully understand what differentiates these 2 deformities. This study aims to (1) characterize the radiographic and pedobarographic features commonly encountered in the juvenile bunion and (2) determine which of these radiographic or pedobarographic parameters correlate with patient-reported outcome (PRO) scores at the time of presentation. METHODS: An IRB-approved retrospective analysis of prospectively enrolled patients between 10 and 18 years of age with bunion deformities was performed at a single pediatric institution over a 4-year period. Standardized weight-bearing radiographs were used to determine hallux valgus angle (HVA), intermetatarsal angle, sesamoid position (SP), distal metatarsal articular angle (DMAA), and other radiographic parameters. Pedobarographic analysis was used to determine peak pressure, contact area, contact time, and pressure-time integral within 11 plantar regions. Foot-specific PRO measures were administered at the initial presentation. RESULTS: Thirty-two patients (57 feet) met the inclusion criteria of which56/57 feet (98.2%) had an elevated DMAA (average 21.4degrees±8.9 degrees), and 51/57 (89.4%) had a congruent joint. The DMAA correlated positively with the HVA (r=0.734 P <0.001), intermetatarsal angle (r=0.439 P =0.001), and SP (r=0.627 P <0.001). Pedobarographic analysis (available in 15/32 patients) demonstrated that the HVA correlated with increased second metatarsal head peak pressure (r=0.667 P =0.011) and pressure-time integral (r=0.604 P =0.002), which in turn was strongly correlated with worse PROs. Conversely, increased first metatarsal head contact area correlated with improved PROs. Analysis of radiographic measurements demonstrated that HVA and lateralized SP correlated significantly with worse PRO scores. CONCLUSIONS: Nearly all juvenile bunions have an elevated DMAA and a congruent joint. There is a clear correlation between the severity of radiographic and pedobarographic deformity and worse PRO scores at the time of presentation. We believe that the presence of elevated DMAA is the defining factor that differentiates the juvenile bunion from the deformity typically seen in adults. LEVEL OF EVIDENCE: III.

Dysplasia Epiphysealis Hemimelica in the Lower Extremity.

BACKGROUND: Because of the rarity of dysplasia epiphysealis hemimelica (DEH), little is known about the relationship between disease classification and clinical symptoms or patient outcomes. This studies therefore aims to characterize DEH of the lower extremity and correlate radiographic classification to presenting symptomatology and need for surgical intervention. METHODS: A multi-center, retrospective review of all patients with DEH of the lower extremity over a 47-year period was conducted. Demographic data, presenting complaints, treatments, and symptoms at final follow-up were recorded. Radiographs were reviewed to classify lesions using the Universal Classification System for Osteochondromas (UCSO) and document the presence of solitary or multiple lesions within the involved joint. Correlative statistics were used to determine whether presenting complaints, lesion location or radiographic classification predicted the need for surgery or a pain-free outcome. RESULTS: Twenty-eight patients met inclusion criteria with an average age at presentation of 7.8 years. The ankle was the most commonly affected joint with 20/28 patients (71%) having lesions of the talus, distal tibia, or distal fibula. Patients with chief complaints of pain were more likely to undergo surgery than those with complaints of a mass or deformity ( P =0.03). Ankle lesions were more likely to be managed operatively than those of the hip or knee ( P =0.018) and all 12 patients with talar lesions underwent surgery. Neither the number of lesions nor lesion classification was predictive of surgical intervention or a pain-free outcome after surgery. Patients presenting with pain were more likely to have a pain-free outcome (11/14 patients) after surgery ( P =0.023) whereas all patients presenting with deformity who underwent surgery had pain at final follow-up. CONCLUSIONS: Although no single radiographic characteristic of DEH was predictive of surgical intervention or outcome, painful lesions of the ankle, and lesions of the talus were more likely to be managed operatively. Although surgery does not always result in a pain-free outcome, the operative management of painful lesions was more likely to provide a pain-free outcome than surgery for deformity or a mass.

The Reliability of the AO Spine Upper Cervical Classification System in Children: Results of a Multi-Center Study.

BACKGROUND: There is no uniform classification system for traumatic upper cervical spine injuries in children. This study assesses the reliability and reproducibility of the AO Upper Cervical Spine Classification System (UCCS), which was developed and validated in adults, to children. METHODS: Twenty-six patients under 18 years old with operative and nonoperative upper cervical injuries, defined as from the occipital condyle to the C2-C3 joint, were identified from 2000 to 2018. Inclusion criteria included the availability of computed tomography and magnetic resonance imaging at the time of injury. Patients with significant comorbidities were excluded. Each case was reviewed by a single senior surgeon to determine eligibility. Educational videos, schematics describing the UCCS, and imaging from 26 cases were sent to 9 pediatric orthopaedic surgeons. The surgeons classified each case into 3 categories: A, B, and C. Inter-rater reliability was assessed for the initial reading across all 9 raters by Fleiss's kappa coefficient (kF) along with 95% confidence intervals. One month later, the surgeons repeated the classification, and intra-rater reliability was calculated. All images were de-identified and randomized for each read independently. Intra-rater reproducibility across both reads was assessed using Fleiss's kappa. Interpretations for reliability estimates were based on Landis and Koch (1977): 0 to 0.2, slight; 0.2 to 0.4, fair; 0.4 to 0.6, moderate; 0.6 to 0.8, substantial; and >0.8, almost perfect agreement. RESULTS: Twenty-six cases were read by 9 raters twice. Sub-classification agreement was moderate to substantial with α κ estimates from 0.55 for the first read and 0.70 for the second read. Inter-rater agreement was moderate (kF 0.56 to 0.58) with respect to fracture location and fair (kF 0.24 to 0.3) with respect to primary classification (A, B, and C). Krippendorff's alpha for intra-rater reliability overall sub-classifications ranged from 0.41 to 0.88, with 0.75 overall raters. CONCLUSION: Traumatic upper cervical injuries are rare in the pediatric population. A uniform classification system can be vital to guide diagnosis and treatment. This study is the first to evaluate the use of the UCCS in the pediatric population. While moderate to substantial agreement was found, limitations to applying the UCCS to the pediatric population exist, and thus the UCCS can be considered a starting point for developing a pediatric classification. LEVEL OF EVIDENCE: Level III.

Microwave Synthesis of Au Nanoparticles in the Presence of Tetrahydrothiophenocucurbituril.

The preparation of gold nanoparticles (AuNPs) from tetrachloroauric acid in the presence of tetrahydrothiophenocucurbit[n]uril (THTmQ[n]) has been effectively achieved in a microwave reactor. The reaction was performed in the presence of an excess of the tetrahydrothiopheno function in a partial reductant role, while the remainder formed AuNP-THTmQ[n] conjugates after the reduction was completed with formic acid. An affinity for the AuNPs by the THTmQ[n] was observed in the purification of the NPs via centrifugation, removal of the supernatant and resuspension of the conjugate.

Occurrence of herbicides in the aquatic environment and their removal using advanced oxidation processes: a critical review.

Herbicides are chemicals used globally to kill unwanted plants so as to obtain high agricultural yields and good agricultural products. Herbicides are sometimes transported from the farmlands into water bodies mainly through runoffs. These chemicals are recalcitrant, and their accumulation is hazardous to abiotic and biotic components of the ecosystem. At present, the best alternative technology for elimination of herbicides in water is the usage of advanced oxidation processes (AOPs). The AOPs, which are performed homogeneously or heterogeneously, are capable of breaking down complex pollutants in water into carbon dioxide and mineral compounds. In these processes, ·OH is produced and used for degradation process. It is recommended that the total organic carbon (TOC) produced during degradation reaction be monitored because the ‧OH produced or generated can react to form intermediates before complete mineralisation is achieved. Different kinds of AOPs for degradation of herbicides have their specific advantages as well as limitations. This report shows that AOPs are excellent techniques for degradation of herbicides in aqueous solutions, and the mechanisms showed that herbicides were mineralised. The amount and type of photocatalysts, pH of the medium, surface characteristics of the photocatalysts, doping of the photocatalysts, temperature of the medium, concentration of herbicides, presence of competing ions, intensity and irradiation period, and type of oxidants have great influence on the degradation of herbicides in water. Overall, this report showed that most AOPs could not completely degrade herbicides in water and complete degradation can be achieved by developing novel and robust AOPs that will completely mineralise herbicides in water-this will pave way for water and environmental safety.