Search

The Hammersmith Infant Neurological Examination (HINE) is a standardized assessment that identifies early signs of cerebral palsy (CP). In practice, the clinician performs this assessment in its entirety, yielding a global score. This study aimed to investigate the individual HINE subscores and "asymmetries" as predictive indicators of CP. In this retrospective nested case-control study, a pediatric neurologist performed the HINE on a cohort of three- to four-month-old former neonatal intensive care unit infants. The infants' neurodevelopmental outcomes were determined by chart review when they were aged two to three years. We performed univariate and multivariable logistic regression analyses to yield the accuracy of the global HINE score, HINE subscores, and "asymmetries" in classifying infants with and without CP. Of the 108 infants on whom HINE was performed, 50 were either discharged due to normal developmental progress or were lost to follow-up. Of the remaining 58 subjects, 17 had CP and 41 did not. Receiver operator characteristic (ROC) curves of univariate models yielded the following area under the curve (AUC) scores: global HINE score (AUC = 0.75), "reflexes and reactions" (AUC = 0.80), "cranial nerve function" (AUC = 0.76), "asymmetries" (AUC = 0.75), and "movements" (AUC = 0.71). The ROC for our multivariable model (AUC = 0.91) surpassed the global HINE score's predictive value for CP. The weighted combination of HINE subscores and "asymmetries" outperforms the global HINE score in predicting CP. These findings suggest the need for revisiting HINE, but further validation with a larger dataset is required. [ABSTRACT FROM AUTHOR]

Ultrasonography (US) is the preferred imaging for suspected pediatric appendicitis. We hypothesize that children with elevated Body-Mass-Index-for-age percentile (BMIP) may be more likely to have an inaccurate or equivocal (IE) US. After IRB approval, a four-year review was performed on pediatric patients evaluated for appendicitis by US. The CDC BMIP Calculator was used. IE subgroups were analyzed together for comparison against the accurate group. 1059 patients were included: median age 11.3 years (IQR: 8.2, 14.6), 506 (47.8%) males. Median BMIP was 65.9 (IQR: 33.9, 89.6). US accurately diagnosed 857 (80.9%), incorrectly diagnosed 76 (7.2%), 126 (11.9%) were equivocal. Overall sensitivity was 0.85, specificity 0.96, PPV 0.93 and NPV 0.91. Obese children (BMIP ≥95%), had higher odds of IE US (OR: 1.86, 95% CI: 1.28, 2.70; p = 0.001). When analyzed by sex, risk increased in obese males (OR: 2.55, 95% CI:1.53, 4.24; p = 0.0003) but normalized in obese females (OR: 1.30, 95% CI:0.74, 2.28; p = 0.35). An elevated BMIP may increase difficulty in visualizing the appendix, resulting in inaccurate or equivocal findings. This risk is seen specifically in obese males. If US findings do not correlate with clinical assessment in obese children with abdominal pain, further evaluation may be warranted. [ABSTRACT FROM AUTHOR]

In certain pathologies, mitral valve repair is complicated by a paucity of tissue caused by fibrosis or destruction. Utilization of autologous pericardium for leaflet augmentation may be the only option to repair these valves. We present the midterm results of mitral valve leaflet augmentation with glutaraldehyde-fixed autologous pericardium. One hundred thirty consecutive patients undergoing mitral valve repair with glutaraldehyde-fixed pericardial augmentation of leaflets were followed up clinically and by echocardiography at 6-month intervals. Mean age was 24.8 years (range 2-64). The etiology was rheumatic in 75.3%, indeterminate in 8.4%, and other in 16.1%. Out of the rheumatics, 57.1%, 24.4%, and 18.3% had combined mitral stenosis and mitral regurgitation, isolated mitral regurgitation, and mitral stenosis, respectively. About 21.5% had a recent history of rheumatic activity. Eight were operated emergently for intractable heart failure. Majority of the patients required repair of multiple components of the mitral valve apparatus. Leaflet peeling was done in 52.3%. Pericardial patch augmentation of anterior mitral leaflet, posterior mitral leaflet, or both were carried out in 61.5%, 34.6%, and 3.8% patients respectively. Sixty percent got chordal procedures, while 92.3% got annuloplasty. There were no deaths during the mean follow-up period of 28 months. Ninety-three percent of our patients were in New York Heart Association class I and II on follow-up. There were 11 repair failures. Seven patients underwent a reoperation, while 4 patients are being managed conservatively (reoperation rate 5.38%). Augmentation of mitral valve leaflets with autologous pericardium allows many significantly fibrosed and destroyed valves to be reliably repaired with good midterm durability and hemodynamics. [ABSTRACT FROM AUTHOR]

The demanding nature of caregiving and limited social support can lead to informal carers experiencing loneliness, which can impact their well-being and overall health service use (HSU). The study aims to examine the association between loneliness with HSU and Health state utility values among informal carers in Australia. Data were derived from three waves (2009, 2013, and 2017) of the nationally representative longitudinal Household Income and Labour Dynamics of Australia (HILDA) survey, focusing on adult informal carers. Outcome measures included visits to the General Practitioner, the number of hospital admissions, and the SF-6D score. Generalized Estimating Equations (GEE) analysis was conducted to explore the associations between loneliness and HSU, as well as loneliness and utility values (based on SF-6D) while adjusting for age, sex, education, marital status, income, and physical/mental health conditions. After controlling for covariates, lonely carers reported lower utility values (IRR = 0.91, 95%CI [0.89, 0.93], p < 0.001) compared to non-lonely carers. Lonely carers reported a higher number of GP visits (IRR = 1.18, 95% CI [1.04, 1.36], p < 0.05) as well as a higher likelihood of visiting specialists (AOR = 1.31, p = 0.046) and hospital doctors (AOR = 1.42, p = 0.013) compared to the non-lonely carers. The findings of this study highlight the relationship between loneliness on both healthcare utilization and carers' overall well-being. Addressing loneliness through targeted interventions and social support systems can help improve health outcomes and potentially reduce the overall healthcare costs among informal carers in Australia. • Loneliness is linked to lower health state utility values among informal carers. • Lonely informal carers tend to meet GPs and specialist more frequently. • Interventions targeting to reduce loneliness can reduce cost and improve wellbeing. [ABSTRACT FROM AUTHOR]

Cervical cancer is caused by certain types of Human Papillomavirus (HPV) and is preceded by a long pre-cancerous stage of Cervical Intra-epithelial Neoplasia (CIN). Cervical cancer can be prevented by successful introduction of an HPV immunization programme and screening using HPV testing, cytology and colposcopy. In the last decade and going forward, significant progress has been made in cervical screening methodologies, which are likely to further reduce the disease burden of cervical cancer and morbidity associated with CIN. We now have a better understanding of the natural history of HPV infection and progression of CIN. Three vaccines are currently available and immunization programmes are well established in developed and developing countries. Cytology screening is currently done using liquid based cytology with additional HPV testing for triage and test of cure. This will be replaced in the UK, in the near future, with primary HPV screening. New adjunctive technologies to Colposcopy are now available that improve the sensitivity of Colposcopy and have the potential to reduce the morbidity associated with CIN. [ABSTRACT FROM AUTHOR]

Traditionally conceived of and studied as a disorder of cognitive and emotional functioning, schizophrenia (SZ) is also characterized by alterations in bodily sensations. These have included subjective reports based on self-evaluations and/or clinical observations describing motor, as well as sensory-based corporeal anomalies. There has been, however, a paucity of objective methods to capture and characterize bodily issues in SZ. Here we present a new research method and statistical platform that enables precise evaluation of peripheral activity and its putative contributions to the cognitive control of visuomotor actions. Specifically , we introduce new methods that facilitate the individualized characterization of the function of sensory-motor systems so as to detect if subjects perform outside of normal limits. In this paper, we report data from a cohort of patients with a clinical diagnosis of SZ. First, we characterize neurotypical subjects performing a visually guided pointing task that requires visuomotor transformations, multi-joint coordination, and the proper balance between different degrees of intent, among other factors. Then we measure SZ patients against the normative statistical ranges empirically determined. To this end, we examine the stochastic signatures of minute fluctuations in motor performance (micro-movements) of various velocity- and geometric-transformation-dependent trajectory parameters from the hand motions. These include the motions en-route to the target as well as spontaneous (without instructions) hand-retractions to rest. The comparisons reveal fundamental differences between SZ patients and controls. Specifically, velocity-dependent signatures show that SZ patients move significantly slower than controls with more noise and randomness in their moment-by-moment hand micro-motions. Furthermore, the normative geometric-dependent signatures of deliberateness are absent from the goal-directed reaches in SZ, but present within normative ranges in their spontaneous hand retractions to rest. Given that the continuous flow of micro-motions contributes to internally sensed feedback from self-produced movements, it is highly probable that sensory-motor integration with externally perceived inputs is impaired. Such impairments in this SZ cohort seem to specifically alter the balance between deliberate and spontaneous control of actions. We interpret these results as potential indexes of avolition and lack of agency and action ownership. We frame our results in the broad context of Precision Psychiatry initiatives and discuss possible implications on the putative contributions of the peripheral nervous system to the internal models for the cognitive control of self-produced actions in the individual with a clinical diagnosis of SZ. [ABSTRACT FROM AUTHOR]

The modern cardiac intensive care unit (CICU) cares for increasingly complex patients with multiorgan system dysfunction, often including respiratory failure. Preliminary data suggests that having an automatic critical care consultation for patients on mechanical ventilation may improve outcomes. Whether this dedicated consultation also improves outcomes in a closed CICU staffed by heart failure physicians is unknown. We performed a single-center retrospective study of consecutive patients who were admitted to the CICU between 2010-2017 and required mechanical ventilation for more than 24 hours. In 2014, the CICU became closed and staffed primarily by a heart failure physician. At that time, a policy of automatic critical care consultation for all mechanically ventilated patients was also implemented. We collected data on demographics and hospital-course for patients admitted before and after these changes in order to compare mortality and ventilation/intubation outcomes. We controlled for baseline comorbidities using multiple linear and logistic regression analyses. There were 581 patients included in the study; 159 admitted before 2014 and 422 after 2014. The most common reason for intubation in both groups was hypoxic respiratory failure (57.3% vs 48.8%, p=0.20) followed by need for airway protection (26.4% vs. 37.5%, p=0.08). Those admitted after 2014 had a significant reduction in 30-day mortality (OR 0.49, p=0.007), 1-year mortality (OR 0.502, p=0.02) and a reduction in re-intubations (OR 0.395, p=0.0008). They were also much more likely to have received critical care consultation (76.2% vs 31.4% before 2014, P<0.00001). Overall, patients who received consultations were more likely to remain on mechanical ventilation longer in the CICU (1.8 more days, p=0.003) and to require more re-intubations (OR 4.06, p=0.0005). Even among patients admitted after 2014, critical care consultation in the CICU had no added effect on mortality or ventilator outcomes and was again associated with an excess of 1.6 days of mechanical ventilation (p = 0.03). Cardiac patients requiring mechanical ventilation had significantly improved mortality and airway outcomes when cared for by a dedicated heart failure specialist. Automatic critical care consultation added no additional improvement in mortality and was associated with longer durations of mechanical ventilation and more re-intubations. Further prospective studies in ventilated patients in CICUs will be needed to continue to improve care for this population. [ABSTRACT FROM AUTHOR]

Objective To review the published literature assessing the efficacy and safety of mitomycin-C (MMC) as an adjunctive treatment in corneal surface excimer laser ablation procedures. Methods Literature searches of the PubMed and Cochrane Library databases were last conducted on August 19, 2014, without language or date limitations. The searches retrieved a total of 239 references. Of these, members of the Ophthalmic Technology Assessment Committee Refractive Management/Intervention Panel selected 26 articles that were considered to be of high or medium clinical relevance, and the panel methodologist rated each article according to the strength of evidence. Ten studies were rated as level I evidence, 5 studies were rated as level II evidence, and the remaining 11 studies were rated as level III evidence. Results The majority of the articles surveyed in this report support the role of MMC as an adjunctive treatment in surface ablation procedures. When MMC is applied in the appropriate concentration and confined to the central cornea, the incidence of post-surface ablation haze is decreased. Although a minority of studies that evaluated endothelial cell density (ECD) reported an MMC-related decrease in ECD, no clinical adverse outcomes were reported. Conclusions Over the past 15 years, the use of MMC during surgery in surface ablation has become widespread. There is good evidence of the effectiveness of MMC when used intraoperatively as prophylaxis against haze in higher myopic ablations. Although there are reports of decreased endothelial counts after the administration of MMC during surgery, the clinical significance of this finding remains uncertain, because no adverse outcomes were reported with as much as 5 years of follow-up. Optimal dosage, effectiveness as prophylaxis in lower myopic and hyperopic ablations, and long-term safety, particularly in eyes with reduced corneal endothelial cell counts from prior intraocular surgery, have yet to be established. [ABSTRACT FROM AUTHOR]

Protein palmitoylation describes the posttranslational modification of cysteines by a thioester-linked long-chain fatty acid. This modification is critical for membrane association, spatial organization, and the proper activity of hundreds of membrane-associated proteins. Palmitoylation is continuously remodeled, both by spontaneous hydrolysis and enzyme-mediated de-palmitoylation. Bioorthogonal pulse-chase labeling approaches have highlighted the role of protein thioesterases as key regulators of palmitoylation dynamics. Importantly, thioesterases are critical for regulating the spatial organization of key oncogenic proteins, such as Ras GTPases. New inhibitors, probes, and proteomics methods have put a spotlight on this emerging posttranslational modification. These tools promise to advance our understanding the enzymatic regulation of dynamic palmitoylation, and present new opportunities for drug development. [ABSTRACT FROM AUTHOR]

Abstract: Human protein isoprenylcysteine carboxyl methyltransferase (hIcmt) is the enzyme responsible for the α-carboxyl methylation of the C-terminal isoprenylated cysteine of CaaX proteins, including Ras proteins. This specific posttranslational methylation event has been shown to be important for cellular transformation by oncogenic Ras isoforms. This finding led to interest in hIcmt inhibitors as potential anti-cancer agents. Previous analog studies based on N-acetyl-S-farnesylcysteine identified two prenylcysteine-based low micromolar inhibitors (1a and 1b) of hIcmt, each bearing a phenoxyphenyl amide modification. In this study, a focused library of analogs of 1a and 1b was synthesized and screened versus hIcmt, delineating structural features important for inhibition. Kinetic characterization of the most potent analogs 1a and 1b established that both inhibitors exhibited mixed-mode inhibition and that the competitive component predominated. Using the Cheng–Prusoff method, the K i values were determined from the IC50 values. Analog 1a has a K IC of 1.4±0.2μM and a K IU of 4.8±0.5μM while 1b has a K IC of 0.5±0.07μM and a K IU of 1.9±0.2μM. Cellular evaluation of 1b revealed that it alters the subcellular localization of GFP-KRas, and also inhibits both Ras activation and Erk phosphorylation in Jurkat cells. [Copyright &y& Elsevier]

Abstract: Human isoprenylcysteine carboxyl methyltransferase (hIcmt) is a promising anticancer target as it is important for the post-translational modification of oncogenic Ras proteins. We herein report the synthesis and biochemical activity of 41 farnesyl-cysteine based analogs versus hIcmt. We have demonstrated that the amide linkage of a hIcmt substrate can be replaced by a sulfonamide bond to achieve hIcmt inhibition. The most potent sulfonamide-modified farnesyl cysteine analog was 6ag with an IC50 of 8.8±0.5μM for hIcmt. [Copyright &y& Elsevier]

Objective: To determine whether the duration of mitomycin C (MMC) 0.02% application affects visual outcome or the incidence of subepithelial haze in patients undergoing photorefractive keratectomy (PRK) with prophylactic administration of MMC. Design: Retrospective, comparative case series. Participants: Two hundred sixty-nine eyes undergoing PRK. Methods: This was a retrospective comparative case series that included 269 eyes that underwent PRK with prophylactic MMC application for 120 seconds (group 1, n = 74), 60 seconds (group 2, n = 36), or 12 seconds (group 3, n = 159). The mean preoperative spherical equivalent was –6.49 diopters (D) in group 1, –6.77 D in group 2, and –7.10 D in group 3. Photorefractive keratectomy was performed using a modified nomogram. All eyes received a single intraoperative application of MMC (0.02%) after laser ablation for the above specified durations. Main Outcome Measures: Best-corrected visual acuity and corneal haze score. Results: Best-corrected visual acuity was 20/23 in group 1, 20/20 in group 2, and 20/21 in group 3. The mean haze score±standard deviation (scale, 0.00–4.00) was 0.11±0.31 in group 1, 0.14±0.28 in group 2, and 0.07±0.20 in group 3 throughout a mean follow-up of 31 months in group 1, 16 months in group 2, and 10 months in group 3. No eyes had a haze score of more than 1.00. Conclusions: There was no statistically significant difference in postoperative best-corrected visual acuity or haze scores among the 3 groups. Administration of prophylactic MMC 0.02% for 12 seconds after PRK seems to be equally efficacious for haze prophylaxis when compared with longer application times of 60 and 120 seconds. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. [Copyright &y& Elsevier]

Driveline exit site infections (DLESi) are common complications of left ventricular assist device (LVAD) therapy. Rarely, non-tuberculosis mycobacteria (NTB) cause such infections. We present a case showing successful treatment of a DLESi due to Mycobacterium chelonae which first became clinically apparent after orthotopic heart transplant (OHT). A 61-year-old male with a dilated cardiomyopathy received a Heartmate 3 LVAD followed 4 years later by OHT. Prior to OHT, no infections were reported. Two months after OHT, an abdominal wall abscess at the former driveline exit site was treated with incision and drainage. Abdominal wound drainage continued, with appearance of satellite lesions and chest wall nodules. Although initial cultures were negative, wound cultures collected 3 months later, grew M. chelonae. For rare NTM related DLESi, a standardized regimen is not established. Hence, commonly used macrolide, quinolone, and linezolid were started. Azithromycin was initially chosen over the more frequently studied clarithromycin due to the latter's interaction with tacrolimus. Linezolid was stopped due to pancytopenia and the ensuing susceptibility report showed quinalone resistance. As a result, the patient was functionally on macrolide monotherapy which led to a recurrence of nodules. Thus, multiple antibiotic regimens were started in succession (Figure). The final clofazimine, azithromycin, and tigecycline based regimen was clinically effective, but caused intolerable diarrhea that led to self-discontinuation of treatment after ∼9 months of therapy. He remains asymptomatic 1-year since antibiotic termination. Picking an antibiotic regimen for rare, difficult-to-treat NTB related DLESi involves using the sensitivity analysis while accounting for drug-drug interactions with immunosuppressive medications. Our case demonstrates efficacy of a macrolide and clofazimine based regimen for treatment of a LVAD associated NTB infection in an OHT patient. [ABSTRACT FROM AUTHOR]

Abstract: The finding of a pelvic mass may present in a female of any age. All pelvic masses do not originate from the genital tract. This article presents the various age- and site-specific aetiologies. A pelvic mass may present with a wide spectrum of symptoms and not all will be symptomatic. Ultrasound is the least invasive and most cost-effective diagnostic tool. The role and accuracy of other imaging modalities are also described. Specific tumour markers and risk of malignancy indices will help to predict malignancy. Fortunately, most masses are associated with a benign pathology. Fibroids and ovarian neoplasms often present as a pelvic mass. This article provides up-to-date information on the diagnosis and management of these and other less common gynaecological conditions that present as a pelvic mass. [Copyright &y& Elsevier]

Abstract: The effects of cobalt chloride on heart rate, blood pressure, ventilatory frequency and opercular pressure amplitude in channel catfish, Ictalurus punctatus were measured to evaluate the potential of cobalt as a histochemical probe to study mechanisms of oxygen chemoreception, as well as assess the general effects of cobalt on the cardioventilatory physiology of fishes. Cobalt, like cyanide, has been previously used to stimulate oxygen chemoreceptors and hypoxic reflexes in mammals but there is little information on the cardioventilatory effects of cobalt on fish. Catfish were exposed to increasing concentrations (1–20 mg/kg) of cobalt in the water (external) or injections into the dorsal aorta (internal) and the cardioventilatory effects recorded. Mean arterial pressure showed a significant, dose-dependent increase in response to cobalt injections. Heart rate increased slowly, but significantly after cobalt injections but the magnitude of change was not dose-dependent. There was a small increase in ventilatory rate but no effect on amplitude. External cobalt had similar effects but the responses were weaker. Although cobalt stimulated some cardioventilatory reflexes the pattern and magnitude of the responses were noticeably different from those of cyanide and hypoxia. The results suggest that the cardioventilatory reflexes stimulated by cobalt were not mediated by O2-sensitive chemoreceptors and that cobalt is not an effective O2 receptor stimulant in fishes. [Copyright &y& Elsevier]

Given the correlation between many human diseases and mis-regulated transcription, there is a growing need for molecules that can inhibit or mimic key interactions between transcriptional activators and their binding partners. Because transcriptional activators typically participate in many different protein–protein binding events, the identification of small molecules or peptides that specifically target individual interactions represents a significant challenge. In spite of this, several small molecules that preferentially inhibit particular complexes of transcriptional activators or mimic the function of activators have recently been reported. These molecules serve as excellent mechanistic tools for studying transcription and, further, have outstanding therapeutic potential. [Copyright &y& Elsevier]

Characterizing the viscoelastic behavior of neonatal peripheral nerves is critical in understanding stretch-related peripheral nerve injuries (PNIs) in neonates. This study investigated the in-vitro viscoelastic stress relaxation response of neonatal piglet brachial plexus (BP) and tibial nerves at two different strain levels (10% and 20%) and stress relaxation testing durations (90- and 300-seconds). BP and tibial nerves from 20 neonatal piglets were harvested and pre-stretched to either 10% or 20% strain at a dynamic rate of 100 mm/min to simulate conditions, such as shoulder dystocia, that may lead to stretch-related PNIs in neonates. At constant strain, the reduction in stress was recorded for 90- or 300-seconds. The biomechanical data were then fit to a viscoelastic model to acquire the short- and long-term stress relaxation time-constants. Though no significant differences in the degree of stress relaxation were found between the two tested strain levels after 90 seconds in both nerve types, reduction in stress was moderately greater (p = 0.056) at 10% strain than at 20% for BP after 300 seconds. The reduction in stress was significantly higher in nerves subjected to a 300 second testing duration than 90 second for both strain levels and nerve types. When comparing BP and tibial nerve stress relaxation response, BP nerve relaxed significantly more than tibial at both strain levels after 90 seconds, but no significant differences were observed after 300 seconds. Our results confirm that neonatal peripheral nerve tissue is highly viscoelastic. These novel biomechanical data can be incorporated into finite element and computational models studying neonatal PNIs. [ABSTRACT FROM AUTHOR]

We characterized basement membrane zone (BMZ) autoantigens targeted by autoantibodies (AAb) from patients with cicatricial pemphigoid. Serum from a patient with severe oral cicatricial pemphigoid contained IgG anti-BMZ AAb. The AAb labeled a lower BMZ component on salt-split skin and localized to the lower lamina lucida/lamina densa by direct and indirect immunoelectron microscopy (HEM) but did not label blood vessels. The AAb did not react with EHS laminin-1 and type IV collagen, pepsinized human type IV collagen, recombinant entactin, or NC1 domain of type VII collagen by dot blotting and western blotting. We focused our studies on the laminin family, as laminin-5 was identified as an autoantigen in cicatricial pemphigoid. Culture-conditioned media from normal keratinocytes (containing laminin-6 and laminin-5) and JEB keratinocytes (containing laminin-6 but not laminin-5) were studied by western blotting. Under nonreducing conditions, the patient's AAb recognized a 600-kDa protein (laminin-6) intensely and a 400-kDa protein (laminin-5) weakly in normal keratinocyte medium even though abundant laminin-5 was present. In JEB keratinocyte medium, however, the 600-kDa protein (laminin-6) alone was recognized by the patient's AAb. The AAb also immunolabeled BMZ of JEB skin that lacked laminin-5. The AAb from this patient and two other patients with anti-laminin-5 cicatricial pemphigoid immunoprecipitated both laminin-6 an4 laminin-5. Taken together, the results of IEM, non-reducing western blotting, immunoprecipitation, and JEB skin BMZ immunolabeling indicate that laminin-6, as well as laminin-5, is identified by the AAb from a subset of cicatricial pemphigoid patients. We propose the name "anti-laminin cicatricial pemphigoid" for this subset. [ABSTRACT FROM AUTHOR]

Abstract: There is tremendous interest in developing activator artificial transcription factors that functionally mimic endogenous transcriptional activators for use as mechanistic probes, as components of synthetic cell circuitry, and in transcription-targeted therapies. Here, we demonstrate that a phage display selection against the transcriptional activation domain binding motif of the coactivator Tra1(TRRAP) produces distinct sequences that function with similar binding modes and potency as natural activators. These findings set the stage for binding screens with small molecule libraries against TAD binding motifs to yield next-generation small molecule TADs. [Copyright &y& Elsevier]

Actinobacillus actinomycetemcomitans is a microaerophilic, fastidious Gram-negative rod that most commonly causes periodontitis and odontogenic infections. We report the first case of an epidural abscess and osteomyelitis due to this organism resulting from self-extraction of carious teeth. The patient responded to surgical debridement and prolonged antimicrobial therapy with intravenous ceftriaxone. [Copyright &y& Elsevier]

Chromatin organization is highly dynamic and modulates DNA replication, transcription, and chromosome segregation. Condensin is essential for chromosome assembly during mitosis and meiosis, as well as maintenance of chromosome structure during interphase. While it is well established that sustained condensin expression is necessary to ensure chromosome stability, the mechanisms that control its expression are not yet known. Herein, we report that disruption of cyclindependent kinase 7 (CDK7), the core catalytic subunit of CDKactivating kinase, leads to reduced transcription of several condensin subunits, including structural maintenance of chromosomes 2 (SMC2). Live and static microscopy revealed that inhibiting CDK7 signaling prolongs mitosis and induces chromatin bridge formation, DNA double-strand breaks, and abnormal nuclear features, all of which are indicative of mitotic catastrophe and chromosome instability. Affirming the importance of condensin regulation by CDK7, genetic suppression of the expression of SMC2, a core subunit of this complex, phenocopies CDK7 inhibition. Moreover, analysis of genome-wide chromatin conformation using Hi-C revealed that sustained activity of CDK7 is necessary to maintain chromatin sublooping, a function that is ascribed to condensin. Notably, the regulation of condensin subunit gene expression is independent of superenhancers. Together, these studies reveal a new role for CDK7 in sustaining chromatin configuration by ensuring the expression of condensin genes, including SMC2. [ABSTRACT FROM AUTHOR]

: ObjectiveTo evaluate the relationship between videokeratographic keratoconus screening programs and Orbscan II topography.: DesignProspective, observational case series and instrument validation study.: ParticipantsSixty consecutive eyes with suspicious videokeratography (TMS-1, Tomey Technology, Waltham, MA) were evaluated before undergoing laser in situ keratomileusis (LASIK) surgery. A control group of 50 consecutive eyes without suspicious features by videokeratography was also evaluated.: MethodsKeratoconus screening programs, using the Rabinowitz and Klyce/Maeda methods and Orbscan II (Bausch & Lomb, Claremont, CA) topographies were performed on these patients.: Main outcome measuresSpecific parameters evaluated on the Orbscan II topographies were anterior elevation, posterior elevation, and thinnest pachymetry.: ResultsCompared with a control group of patients without suspicious videokeratography, there was a statistically significant difference in the mean posterior elevation and mean anterior elevation in the groups with positive keratoconus testing with the Rabinowitz or Klyce/Maeda methods. For patients who met both the Rabinowitz and Klyce/Maeda criteria for keratoconus, the mean posterior elevation was 44 ± 2.5 μm compared with a posterior elevation of 21 ± 0.6 μm for the control group. There was no statistically significant difference in the mean thinnest pachymetry between the control group and all keratoconus suspect groups.: ConclusionsPatients with positive keratoconus screening tests have higher anterior and posterior elevation on Orbscan II topography. When used in combination with videokeratography, the Orbscan II topography system may be helpful in identifying patients who are potentially at high risk for developing ectasia after LASIK. [Copyright &y& Elsevier]

Objectives: To update the existing evidence to identify specific barriers to initiation of opioid substitution therapy (OST) for those with opioid use disorder (OUD).Methods: The review follows Preferred Reporting Items for Systematic Reviews andMeta-Analyses (PRISMA) guidelines. Six databases were initially searched in November 2019, with the search updated on 11 November 2020, for qualitative or quantitative studies reporting the barriers to initiating OST from the client with OUD perspective. Thematic analysis of the barriers to OST was undertaken to determine barrier themes and subthemes.Results: There were 37 studies included in the review; 18 were qualitative, 15 were quantitative and four were mixed methods. The barrier themes identified were stigma and fear, regulatory, logistical, attitudinal and social factors. Within these barrier themes 19 barrier subthemes were identified. The most reported OST barrier subthemes were negative treatment perceptions, cost, stigma and lack of flexibility.Conclusion: This review discusses important barriers to OST and examines reported barriers from the client perspective. OST guidelines and programs would benefit by introducing programs that reduce stigma, increase treatment knowledge and health literacy, reduce treatment costs, increase treatment flexibility and allow for easier treatment access. [ABSTRACT FROM AUTHOR]