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Objective Pseudarthrosis and adjacent segment degeneration (ASD) are 2 common complications after multilevel anterior cervical discectomy and fusion (ACDF). We aim to identify the potential biomechanical factors contributing to pseudarthrosis and ASD following 3-level ACDF using a cervical spine finite element model (FEM). Methods A validated cervical spine FEM from C2 to C7 was used to study the biomechanical factors in cervical spine intervention. The FEM model was used to simulate a 3-level ACDF with intervertebral spacers and anterior cervical plating with screw fixation from C4 to C7. The model was then constrained at the inferior nodes of the T1 vertebra, and physiological loads were applied at the top vertebra. The pure moment load of 2 Nm was applied in flexion, extension, and lateral bending. A follower axial force of 75 N was applied to reproduce the weight of the cranium and muscle force, was applied using standard procedures. The motion-controlled hybrid protocol was utilized to comprehend the adjustments in the spinal biomechanics. Results Our cervical spine FEM demonstrated that the cranial adjacent level (C3–4) had significantly more increase in range of motion (ROM) (+90.38%) compared to the caudal adjacent level at C7–T1 (+70.18%) after C4–7 ACDF, indicating that the cranial adjacent level has more compensatory increase in ROM than the caudal adjacent level, potentially predisposing it to earlier ASD. Within the C4–7 ACDF construct, the C6–7 level had the least robust fixation during fixation compared to C4–5 and C5–6, as reflected by the smallest reduction in ROM compared to intact spine (-71.30% vs. -76.36% and -77.05%, respectively), which potentially predisposes the C6–7 level to higher risk of pseudarthrosis. Conclusion Biomechanical analysis of C4–7 ACDF construct using a validated cervical spine FEM indicated that the C3–4 has more compensatory increase in ROM compared to C7–T1, and C6–7 has the least robust fixation under physiological loads. These findings can help spine surgeons to predicate the areas with higher risks of pseudarthrosis and ASD, and thus developing corresponding strategies to mitigate these risks and provide appropriate preoperative counseling to patients.

Objective To examine existing literature and pool the data to determine the relative odds ratio of “adding-on” (AO) based on various reported criteria for lower instrumented vertebra (LIV) selection in Lenke type 1A and 2A curves. Methods Using electronic databases, studies reporting on AO and LIV selection in Lenke type 1A and 2A curves were identified. Studies were excluded if they failed to meet the following criteria: ≥ 30 patients, Lenke type 1A or 2A curves, thoracic-only fusions, and inclusion of outcome differences in AO and non-AO groups. Review articles, letters, and case reports were excluded. Results Six studies were identified reporting on 732 patients with either Lenke type 1A or 2A curves treated with thoracic-only fusions. Five different landmarks were used for LIV selection in these studies including the stable vertebra (SV) -1, end vertebra (EV) +1, neutral vertebra (NV), touched vertebra (TV), and substantially touched vertebra (STV) versus nonsubstantially touched vertebra (nSTV) +1. The pooled odds ratios of AO for choosing LIV at levels above the afore landmarks (i.e., ending the construct “short”) versus at the landmarks were 2.59 (SV-1), 2.43 (EV+1), 3.05 (NV), 3.40 (TV), and 4.52 (STV/nSTV+1), all at 95% confidence interval. Conclusion Five landmarks shared a similar characteristic in that the incidence of AO was significantly higher if the LIV was proximal to the chosen landmark. In addition, choosing STV/(nSTV+1) as the LIV have the lowest absolute risk of AO and the greatest risk reduction. If additional levels were fused (i.e., LIV distal to the landmark), there was no statistically significant benefit in further reducing the risk of AO. Selection of the optimal LIV is a complex issue and spine surgeons must balance the risk of AO with the need for motion preservation in young patients.

Renal cell carcinoma (RCC) commonly metastasizes to the lung, liver, bones, and brain; however, cutaneous metastases remain rare with few reported cases. Since RCCs have the propensity to metastasize to highly vascular areas, the scalp and skin of the head and neck region are likely locations for cutaneous metastases. We report a rare case of a large, exophytic, cauliflower-like, hemorrhagic, metastatic mass of the posterior neck. This is the first reported case of a head and neck cutaneous RCC metastasis treated with endovascular embolization prior to surgical resection. Due to the increased vascularity of RCCs and risk of excessive hemorrhage during resection, adjunctive embolization of cutaneous head and neck metastasis may have a role. Essential characteristics to our treatment strategy are discussed with a review of pertinent literature.

Due to the highly mobile nature of the cervical spine, and the fact that most magnetic resonance imagings (MRIs) and computed tomography scans are obtained only in one single position, dynamic cord compression can be an elusive diagnosis that is often missed and not well-understood. In this context, dynamic MRI (dMRI) has been utilized to improve the diagnostic accuracy of cervical stenosis. We performed a literature review on dynamic cord compression in the context of cervical spondylotic myelopathy (CSM), with particular emphasis on the role of dMRI. Cadaveric studies report that the spinal cord lengthens in flexion and the spinal canal dimension increases, whereas the spinal cord relaxes and shortens in extension and the spinal canal decreases. These changes may lead to biomechanical stress in the spinal cord with movement, especially in patients with critical cervical stenosis. The majority of the studies using dMRI in CSM reported that this imaging modality is more sensitive at detecting cervical cord compression compared to routine MRIs done in a neutral position, especially with the neck in extension. Dynamic MRI was also useful to diagnose dynamic cervical cord compression after laminectomies in patients with clinical deterioration without evident cord compression on neutral static MRI. Finally, dMRI is more sensitive in detecting stenosis in patients with CSM than in those with ossification of the posterior longitudinal ligament (OPLL), likely because OPLL patients often have a more limited range of motion than CSM patients. Thus, dMRI is a promising new tool that can help spine surgeons in diagnosing and treating CSM.

Objective This retrospective cohort study seeks to identify risk factors associated with complications following posterior cervical laminectomy and fusion (PCLF) surgery. Methods Adults undergoing PCLF from 2012 through 2018 at a single center were identified. Demographic and radiographic data, surgical characteristics, and complication rates were compared. Multivariate logistic regression models identified independent predictors of complications following surgery. Results A total of 196 patients met the inclusion criteria and were included in the study. The medical, surgical, and overall complication rates were 10.2%, 23.0%, and 29.1% respectively. Risk factors associated with medical complications in multivariate analysis included impaired ambulation status (odds ratio [OR], 2.27; p=0.02) and estimated blood loss over 500 mL (OR, 3.67; p=0.02). Multivariate analysis revealed preoperative narcotic use (OR, 2.43; p=0.02) and operative time (OR, 1.005; p=0.03) as risk factors for surgical complication, whereas antidepressant use was a protective factor (OR, 0.21; p=0.01). Overall complication was associated with preoperative narcotic use (OR, 1.97; p=0.04) and higher intraoperative blood loss (OR, 1.0007; p=0.03). Conclusion Preoperative narcotic use and estimated blood loss predicted the incidence of complications following PCLF for CSM. Ambulation status was a significant predictor of the development of a medical complication specifically. These results may help surgeons in counseling patients who may be at increased risk of complication following surgery.

C1 stenosis is often an easily missed cause for cervical myelopathy. The vast majority of cervical myelopathy occurs in the subaxial cervical spine. The cervical canal is generally largest at C1/2, explaining the relatively rare incidence of neurological deficits in patients with odontoid fractures. However, some subjects have anatomical anomalies of the atlas, which may cause stenosis and result in clinical symptoms similar to subaxial cord compression. Isolated pure atlas hypoplasia leading to stenosis is quite rare and may be associated with other anomalies, such as atlas clefts or transverse ligament calcification. It may also be more commonly associated with syndromic conditions such as Down or Turner syndrome. Although the diagnosis can be easily made with a cervical magnetic resonance imaging, the C3/2 spinolaminar test using a lateral cervical plain radiograph is a useful and sensitive tool for screening. Surgical treatment with a C1 laminectomy is generally necessary and any atlantoaxial or occipito-atlanto instability must be treated with spinal stabilization and fusion.

Background: The utilization of the S2 Alar-Iliac (S2AI) screw provides an optimal method of spinopelvic fixation. The free-hand placement of these screws obviates the use of intra-operative fluoroscopy and relies heavily on sacropelvic anatomy; variations of this anatomy could alter the ideal screw trajectory. The S2AI corridor is near several neurovascular structures, thus an accurate trajectory is critical. The reported angles of trajectory vary within the literature and a paucity of data exists on how patient morphometry influences ideal screw trajectory. We sought to examine the relationship between ideal screw trajectory and pelvic parameters. Methods: The records of 99 consecutive patients with degenerative thoracolumbar pathology were reviewed and pelvic parameters including sacral slope, pelvic tilt, and pelvic incidence were measured with preoperative standing radiographs. Using 3-dimensional computed tomography (CT) reconstructions, an ideal S2AI trajectory was defined and anteroposterior (horizontal) and cephalocaudal (sagittal) angles were recorded. Results: Pelvic tilt was found to have a moderate inverse correlation with cephalocaudal screw trajectory (r=-0.467, p-value=0.006). Pelvic incidence and sacral slope had weaker correlations with cephalocaudal screw angle. In subgroup analysis, patients with high pelvic tilt (>20°) had a significantly lower cephalocaudal screw trajectory (24.9 ± 3.7° versus 29.8 ± 2.8°, p-value=

Vein of Galen malformations (VoGMs) are rare vascular malformations resulting from persistent shunting of primitive choroidal vessels into the median prosencephalic vein of Markowski. VoGMs are associated with poor clinical outcome with a reported 76.7% mortality if left untreated. We present an exceedingly rare case of a giant, untreated VoGM measuring 7.8 × 5.5 × 7 cm in a 42-year-old man. The embryologic origin, classification, clinical manifestations, and treatment options of VoGMs are discussed with a review of pertinent literature.

PurposeThe primary correlate to survival and preservation of neurologic function in patients suffering from an acute ischemic stroke is time from symptom onset to initiation of therapy and reperfusion. Communication and coordination among members of the stroke team are essential to maximizing efficiency and subsequently early reperfusion. In this work, we aim to describe our preliminary experience using the Join mobile application as a means to improve interdisciplinary team communication and efficiency.Materials and MethodsWe describe our pilot experience with the initiation of the Join mobile application between July 2015 and July 2016. With this application, a mobile beacon is transported with the patient on the ambulance. Transportation milestone timestamps and geographic coordinates are transmitted to the treating facility and instantly communicated to all treatment team members. The transport team / patient can be tracked en route to the treating facility.ResultsDuring our pilot study, 62 patients were triaged and managed using the Join application. Automated time-stamping of critical events, geographic tracking of patient transport and summary documents were obtained for all patients. Treatment team members had an overall favorable impression of the Join application and recommended its continued use.ConclusionThe Join application is one of several components of a multi-institutional, interdisciplinary effort to improve the treatment of patients with acute ischemic stroke. The ability of the treatment team to track patient transport and communicate with the transporting team may improve reperfusion time and, therefore, improve neurologic outcomes.

Abstract Background The EQ-5D-Y is a generic preference-weighted measure for children and adolescents which was developed within Europe. Two versions exist, the EQ-5D-Y-3L (Y-3L) and EQ-5D-Y-5L (Y-5L). This study aimed to cross-culturally adapt the Y-3L and Y-5L for use in Singapore and to assess the content validity, specifically, the relevance and comprehensiveness of the EQ-5D-Y descriptive system (DS) in Asia. Methods To culturally adapt the instruments, an expert panel consisting of paediatricians and primary school educators were consulted. Modifications suggested by the expert panel were tested via cognitive debriefing interviews with children aged 8–12 in Singapore. To assess the content validity of the EQ-5D-Y DS, interviews were conducted with both healthy (n = 8) and ill children (n = 6) aged 8–15. In the interviews, children discussed their experience with poor health and commented on the comprehensiveness and relevance of the EQ-5D-Y DS. Results The cross-cultural adaptation process led to minor modifications to the UK English Y-3L and Y-5L versions, including using phrases familiar to the local children and adding examples to facilitate understanding. The five health dimensions in the EQ-5D-Y DS were spontaneously elicited when children discussed their experience with poor health. All health dimensions related to poor health elicited from the interviews fell into three broad categories: physical health (e.g. Appetite, Mobility, and Sleep), mental well-being (e.g. Annoyed/Frustrated and Scared/Worried), and social relationships (e.g. Family and Friends). The EQ-5D-Y DS was generally found to be relevant and comprehensive, although some health dimensions that may be relevant to the local population (Social relationship and Appetite) were not covered. Conclusions The UK English EQ-5D-Y instruments were adapted to produce the Singapore English EQ-5D-Y instrument that were comprehensible to local children as young as 8 years old. The EQ-5D-Y DS was generally relevant and comprehensive to measure poor health of local children. Future studies should ascertain the benefits of adding bolt-on items related to social relationships and appetite to the EQ-5D-Y DS.

Abstract Natural products encompass a diverse range of compounds with high impact applications in consumer care, agriculture and most notably, therapeutics. However, despite the expansive chemical repertoire indicated in genomic information of microbes, only a small subset can be obtained under laboratory conditions. To increase accessible chemical space and realize Nature’s full chemical potential, a multi-pronged genetic- and cultivation-based strategy has been employed to activate and upregulate natural product biosyntheses in native and heterologous strains. This data descriptor documents a characterized collection of 2,138 liquid chromatography-tandem mass spectrometry (LC/MS-MS) spectra of fermentation extracts from 54 native actinobacterial strains collected from soil and marine environments in Singapore, and their 459 activated mutants in 3 to 5 media. A total of 743 unique metabolites have been identified, with the activated mutants demonstrating an approximately 2-fold expansion in accessible chemical space over wild type strains. Interrogating this expanded chemical diversity with cheminformatic tools can provide direction for the discovery of novel natural products with desirable functional activity.

Progressive deconstruction is an endovascular technique for aneurysm treatment that utilizes flow diverting stents to promote progressive thrombosis by diverting blood flow away from the aneurysm's parent vessel. While the aneurysm thromboses, collateral blood vessels develop over time to avoid infarction that can often accompany acute parent vessel occlusion. We report a 37-year-old woman with a left distal posterior cerebral artery aneurysm that was successfully treated with this strategy. The concept and rationale of progressive deconstruction are discussed in detail.

The fast development of technology and transportation systems has resulted in a disturbing level of noise pollution over time that requires research and regulatory. Most existing research is deemed ineffective as it primarily focuses on conducting assessments of traffic noise without providing a structured framework for noise mitigation. This study focused on three main stages to monitor road traffic noise in Sungai Long area: (1) examination of traffic features, (2) derivation of noise indices, and (3) evaluation of the influence of traffic noise. Total of four roads were selected with four stations on each road in Bandar Sungai Long to assess the traffic noise impact. The sound level metre (SLM) was used to calculate the noise indices for each road. Besides, peak-hour sessions and off-peak sessions of traffic flow were measured in field measurement to compare the differences in noise conditions. Additionally, based on the measured noise indices, traffic noise index (TNI), noise pollution level (LNP), and expected community response were calculated to reveal the impact of traffic noise. Overall, this study's findings demonstrated that residential areas experiencing traffic noise disturbance, particularly on roads, namely Jalan Bp Satu and Jalan Persiaran SL 7, had exceeded the Malaysian environmental standard. In addition, two optimized methods are proposed which are prohibiting heavy vehicles and a simple noise barrier was designed on Jalan Bp Satu and Jalan Persiaran SL 7. The expected noise level between these two methods had been compared in the discussion part. In summary, prohibiting heavy vehicles on the road is more suitable if the aim is to save cost. However, if reducing traffic noise is a priority and a long-term solution is needed, constructing noise barrier may be a more effective solution.

Abstract Wound is defined as the damage to biological tissues including skin, mucous membranes and organ tissues. The acute wound heals in less than 4 weeks without complications, while a chronic wound takes longer than 6 weeks to heal. Wound healing occurs in 4 phases, namely, coagulation, inflammatory, proliferative and remodeling phases. Triclosan and benzalkonium chloride are commonly used as skin disinfectants in wound healing. However, they cause allergic contact dermatitis and antibiotic resistance. Medicinal plants are widely studied due to the limited availability of wound healing agents. The present review included six commonly available medicinal plants in Malaysia such as Aloe barbadensis Miller, Carica papaya Linn., Centella asiatica Linn., Cymbopogon nardus Linn., Ficus benghalensis Linn. and Hibiscus rosa sinensis Linn. Various search engines and databases were used to obtain the scientific findings, including Google Scholar, ScienceDirect, PubMed Central and Research Gate. The review discussed the possible mechanism of action of medicinal plants and their active constituents in the wound healing process. In addition, their application in nanotechnology and wound dressings was also discussed in detail.

Abstract Halogenation of pyrrole requires strong electrophilic reagents and often leads to undesired polyhalogenated products. Biocatalytic halogenation is a highly attractive approach given its chemoselectivity and benign reaction conditions. While there are several reports of enzymatic phenol and indole halogenation in organic synthesis, corresponding reports on enzymatic pyrrole halogenation have been lacking. Here we describe the in vitro functional and structural characterization of PrnC, a flavin-dependent halogenase that can act on free-standing pyrroles. Computational modeling and site mutagenesis studies identified three key residues in the catalytic pocket. A moderate resolution map using single-particle cryogenic electron microscopy reveals PrnC to be a dimer. This native PrnC can halogenate a library of structurally diverse pyrrolic heterocycles in a site-selective manner and be applied in the chemoenzymatic synthesis of a chlorinated analog of the agrochemical fungicide Fludioxonil.

Abstract Natural products possess significant therapeutic potential but remain underutilized despite advances in genomics and bioinformatics. While there are approaches to activate and upregulate natural product biosynthesis in both native and heterologous microbial strains, a comprehensive strategy to elicit production of natural products as well as a generalizable and efficient method to interrogate diverse native strains collection, remains lacking. Here, we explore a flexible and robust integrase-mediated multi-pronged activation approach to reliably perturb and globally trigger antibiotics production in actinobacteria. Across 54 actinobacterial strains, our approach yielded 124 distinct activator-strain combinations which consistently outperform wild type. Our approach expands accessible metabolite space by nearly two-fold and increases selected metabolite yields by up to >200-fold, enabling discovery of Gram-negative bioactivity in tetramic acid analogs. We envision these findings as a gateway towards a more streamlined, accelerated, and scalable strategy to unlock the full potential of Nature’s chemical repertoire.

Introduction: Differentiating between migraine and COVID-19 headaches is essential for better treatment. Evidence-based research during the COVID-19 pandemic has found that university students are more likely to experience migraine. Migraine can affect academic performance, sleep pattern, social and emotional well-being if left untreated or misdiagnosed. This study aimed to determine the prevalence of migraine symptoms and the association of triggers, coping strategies and clinical characteristics with COVID-19 diagnosis. Methods: This cross-sectional study was conducted across higher educational institutions in Peninsular Malaysia. Convenience sampling was applied to recruit full-time university students. A reliable and validated instrument was used to evaluate demographic data, migraine symptoms, triggers, coping strategies and clinical characteristics of migraine (frequency, intensity, severity and duration) during COVID-19 diagnosis. Results: The response rate was 98.3%, where 485 out of 493 responses were analysed. The prevalence of migraine was 35.9% (n=174). None of the triggers, coping strategies and clinical characteristics of migraine were significantly associated with COVID-19 diagnosis. Conclusion: The university students in Peninsular Malaysia showed a considerable prevalence of migraine symptoms. During the pandemic, the common triggers for existing symptoms were stress and a lack of sleep (combined triggers). The coping strategy adopted by most of the university students was lifestyle changes and in the COVID-19 positive group maladaptive coping strategies were adopted indicating the need for further investigation.

In recent years, CRISPR-Cas toolboxes for Streptomyces editing have rapidly accelerated natural product discovery and engineering. However, Cas efficiencies are oftentimes strain-dependent, and the commonly used Streptococcus pyogenes Cas9 (SpCas9) is notorious for having high levels of off-target toxicity effects. Thus, a variety of Cas proteins is required for greater flexibility of genetic manipulation within a wider range of Streptomyces strains. This study explored the first use of Acidaminococcus sp. Cas12j, a hypercompact Cas12 subfamily, for genome editing in Streptomyces and its potential in activating silent biosynthetic gene clusters (BGCs) to enhance natural product synthesis. While the editing efficiencies of Cas12j were not as high as previously reported efficiencies of Cas12a and Cas9, Cas12j exhibited higher transformation efficiencies compared to SpCas9. Furthermore, Cas12j demonstrated significantly improved editing efficiencies compared to Cas12a in activating BGCs in Streptomyces sp. A34053, a strain wherein both SpCas9 and Cas12a faced limitations in accessing the genome. Overall, this study expanded the repertoire of Cas proteins for genome editing in actinomycetes and highlighted not only the potential of recently characterized Cas12j in Streptomyces but also the importance of having an extensive genetic toolbox for improving the editing success of these beneficial microbes.

Introduction: Differentiating between migraine and COVID-19 headaches is essential for better treatment. Evidence-based research during the COVID-19 pandemic has found that university students are more likely to experience migraine. Migraine can affect academic performance, sleep pattern, social and emotional well-being if left untreated or misdiagnosed. This study aimed to determine the prevalence of migraine symptoms and the association of triggers, coping strategies and clinical characteristics with COVID-19 diagnosis. Methods: This cross-sectional study was conducted across higher educational institutions in Peninsular Malaysia. Convenience sampling was applied to recruit full-time university students. A reliable and validated instrument was used to evaluate demographic data, migraine symptoms, triggers, coping strategies and clinical characteristics of migraine (frequency, intensity, severity and duration) during COVID-19 diagnosis. Results: The response rate was 98.3%, where 485 out of 493 responses were analysed. The prevalence of migraine was 35.9% (n=174). None of the triggers, coping strategies and clinical characteristics of migraine were significantly associated with COVID-19 diagnosis. Conclusion: The university students in Peninsular Malaysia showed a considerable prevalence of migraine symptoms. During the pandemic, the common triggers for existing symptoms were stress and a lack of sleep (combined triggers). The coping strategy adopted by most of the university students was lifestyle changes and in the COVID-19 positive group maladaptive coping strategies were adopted indicating the need for further investigation. [ABSTRACT FROM AUTHOR]