Thoracolumbar Fascia and Lumbar Muscle Stiffness in Athletes with A History of Hamstring Injury.

The purpose of this study was to examine the differences in thoracolumbar fascia (TLF) and lumbar muscle modulus in individuals with and without hamstring injury using shear wave elastography (SWE). Thirteen male soccer players without a previous hamstring injury and eleven players with a history of hamstring injury performed passive and active (submaximal) knee flexion efforts from 0°, 45° and 90° angle of knee flexion as well as an active prone trunk extension test. The elastic modulus of the TLF, the erector spinae (ES) and the multifidus (MF) was measured using ultrasound SWE simultaneously with the surface electromyography (EMG) signal of the ES and MF. The TLF SWE modulus was significantly (p < 0.05) higher in the injured group (range: 29.86 ± 8.58 to 66.57 ± 11.71 kPa) than in the uninjured group (range: 17.47 ± 9.37 to 47.03 ± 16.04 kPa). The ES and MF modulus ranged from 14.97 ± 4.10 to 66.57 ± 11.71 kPa in the injured group and it was significantly (p < .05) greater compared to the uninjured group (range: 11.65 ± 5.99 to 40.49 ± 12.35 kPa). TLF modulus was greater than ES and MF modulus (p < 0.05). Active modulus was greater during the prone trunk extension test compared to the knee flexion tests and it was greater in the knee flexion test at 0° than at 90° (p < 0.05). The muscle EMG was greater in the injured compared to the uninjured group in the passive tests only (p < 0.05). SWE modulus of the TLF and ES and MF was greater in soccer players with previous hamstring injury than uninjured players. Further research could establish whether exercises that target the paraspinal muscles and the lumbar fascia can assist in preventing individuals with a history of hamstring injury from sustaining a new injury.

Low-Medium and High-Intensity Inspiratory Muscle Training in Critically Ill Patients: A Systematic Review and Meta-Analysis.

Background and objectives: Mechanical ventilation is often used in intensive care units to assist patients' breathing. This often leads to respiratory muscle weakness and diaphragmatic dysfunction, causing weaning difficulties. Inspiratory muscle training (IMT) has been found to be beneficial in increasing inspiratory muscle strength and facilitating weaning. Over the years, different protocols and devices have been used. Materials and Methods: The aim of this systematic review and meta-analysis was to investigate the effectiveness of low-medium (LM-IMT) and high-intensity (H-IMT) threshold inspiratory muscle training in critically ill patients. A systematic literature search was performed for randomized controlled trials (RCTs) in the electronic databases Google Scholar, PubMed, Scopus, and Science Direct. The search involved screening for studies examining the effectiveness of two different intensities of threshold IMT in critically ill patients published the last 10 years. The Physiotherapy Evidence Database (PEDro) scale was chosen as the tool to assess the quality of studies. A meta-analysis was performed where possible. Results: Fourteen studies were included in the systematic review, with five of them having high methodological quality. Conclusions: When examining LM-IMT and H-IMT though, neither was able to reach statistically significant improvement in their maximal inspiratory pressure (MIP), while LM-IMT reached it in terms of weaning duration. Additionally, no statistical difference was noticed in the duration of mechanical ventilation. The application of IMT is recommended to ICU patients in order to prevent diaphragmatic dysfunction and facilitate weaning from mechanical ventilation. Therefore, further research as well as additional RCTs regarding different protocols are needed to enhance its effectiveness.

Silver ciprofloxacin (CIPAG): a multitargeted metallodrug in the development of breast cancer therapy.

The anti-proliferative activity of the known metalloantibiotic {[Ag(CIPH)2]NO3∙0.75MeOH∙1.2H2O} (CIPAG) (CIPH = ciprofloxacin) against the human breast adenocarcinoma cancer cells MCF-7 (hormone dependent (HD)) and MDA-MB-231 (hormone independent (HI)) is evaluated. The in vitro toxicity and genotoxicity of the metalloantibiotic were estimated toward fetal lung fibroblast (MRC-5) cells. The molecular mechanism of the CIPAG activity against MCF-7 cells was clarified by the (i) cell morphology, (ii) cell cycle arrest, (iii) mitochondrial membrane permeabilization, and (iv) by the assessment of the possible differential effect of CIPAG on estrogen receptor alpha (ERα) and estrogen receptor beta (ERß) transcriptional activation, applying luciferase reporter gene assay. Moreover, the ex vivo mechanism of CIPAG was clarified by its binding affinity toward calf thymus (CT-DNA).

Is thoracolumbar fascia shear-wave modulus affected by active and passive knee flexion?

The purpose of this study was to examine the effect of passive and active knee flexion efforts on the stiffness of the thoracolumbar (TLF), semitendinosus (STF), and semimembranosus fascia (SMF). Fourteen young healthy males participated in this study. Using ultrasound shear-wave elastography, fascia elastic modulus was measured at rest (passive condition) and during submaximal isometric knee flexion efforts (active condition) with the hip at neutral position and the knee flexed at 0°, 45°, and 90°. Analysis of variance designs indicated that when the knee was passively extended from 90° to 0°, shear modulus of the TLF, SMF, and STF increased significantly (p < 0.05). Similarly, active knee flexion contractions caused a significant increase in TLF, SMF, and STF shear modulus (p < 0.001). Compared to hamstring fascia, the TLF showed greater thickness but a lower shear modulus (p < 0.05) while STF modulus was greater compared that to SMF during active contraction (p < 0.05). These results indicate that exercising the hamstring muscles can remotely influence the stiffness of the fascia which surrounds the lumbar area.

An end-to-end deep learning framework for translating mass spectra to de-novo molecules.

Elucidating the structure of a chemical compound is a fundamental task in chemistry with applications in multiple domains including drug discovery, precision medicine, and biomarker discovery. The common practice for elucidating the structure of a compound is to obtain a mass spectrum and subsequently retrieve its structure from spectral databases. However, these methods fail for novel molecules that are not present in the reference database. We propose Spec2Mol, a deep learning architecture for molecular structure recommendation given mass spectra alone. Spec2Mol is inspired by the Speech2Text deep learning architectures for translating audio signals into text. Our approach is based on an encoder-decoder architecture. The encoder learns the spectra embeddings, while the decoder, pre-trained on a massive dataset of chemical structures for translating between different molecular representations, reconstructs SMILES sequences of the recommended chemical structures. We have evaluated Spec2Mol by assessing the molecular similarity between the recommended structures and the original structure. Our analysis showed that Spec2Mol is able to identify the presence of key molecular substructures from its mass spectrum, and shows on par performance, when compared to existing fragmentation tree methods particularly when test structure information is not available during training or present in the reference database.

Common Carotid Artery Hematoma Following Parathyroid Adenoma FNA.

We present a rare case of a common carotid artery wall hematoma after ultrasound-guided parathyroid fine-needle aspiration. The hematoma was detected within seconds from needle insertion, extending along the common carotid artery wall from the lower neck to the common carotid artery bifurcation, and it was quickly restricted with firm pressure. The patient only reported mild discomfort. A follow-up assessment by a vascular surgeon two hours later showed no signs of ischemic events and complete absorption of the hematoma without further clinical consequences. Physicians performing parathyroid fine-needle aspiration must be aware of this rare complication, which may be easily overlooked. Continuous meticulous sonographic surveillance during the fine needle aspiration procedure is the only way to directly diagnose this complication and apply immediate pressure to restrict it.

Individualized dosimetry in Ru-106 ophthalmic brachytherapy based on MRI-derived ocular anatomical parameters.

PURPOSE: To estimate ocular geometry-related inaccuracies of the dosimetric plan in Ru-106 ophthalmic brachytherapy. METHODS AND MATERIALS: Thirty patients with intraocular lesions were treated with brachytherapy using a Ru-106 plaque-shell of inner radius of 12 mm. Magnetic resonance imaging was employed to determine the external scleral radius at tumor site and the tumor margins. A mathematical model was developed to determine the distance between the external sclera and the internal surface of the plaque associated with the tangential application of the plaque on the treated eye. Differences in delivered dose to the tumor apex, sclera and tumor margins as derived by considering the default eye-globe of standard size (external sclera radius = 12 mm) against the individual-specific eye globe were determined. RESULTS: The radius of external sclera at the tumor site was found to range between 10.90 and 13.05 mm for the patient cohort studied. When the patient specific eye-globe/tumor geometry is not taken into account, the delivered dose was found to be overestimated by 8.1% ± 4.1% (max = 15.3%) at tumor apex, by 1.5% ± 2.8% (max = 5.7%) at anterior tumor margin, by 16.6% ± 7.5% (max = 36.4%) at posterior tumor margin and 8.1% ± 3.8% (max = 13.2%) at central sclera of eyes with lower than the default radius. The corresponding dose overestimations for eyes with higher than the default radius was 13.5% ± 4.3% (max = 22.3%), 1.5% ± 2.8% (max = 5.7%), 12.6% ± 4.5% (max = 20.0%), and 15.1% ± 5.0% (max = 24.4%). CONCLUSIONS: The proposed patient-specific approach for Ru-106 brachytherapy treatment planning may improve dosimetric accuracy. Individualized treatment planning dosimetry may prevent undertreatment of intraocular tumors especially for highly myopic or hyperopic eyes.

Effect of scanning speed, scanning pattern, and tip size on the accuracy of intraoral digital scans.

STATEMENT OF PROBLEM: Currently available intraoral scanning technology makes intraoral scanning quicker and allows the use of smaller scanner tips. However, studies on the influence of scanning speed, tip size, and scanning patterns on scanning accuracy are lacking. PURPOSE: The purpose of this in vitro study was to evaluate the effect of scanning speed, scanning pattern, and scanner tip size on scanning trueness and precision. MATERIAL AND METHODS: A total of 120 complete arch intraoral scans were made with an intraoral scanner (Emerald). The 3 variables were tip size (small and regular), scanning pattern (occlusal first and S-shaped), and scanning speed (slow, regular, and fast). Ten scans for each variable combination were made and exported as standard tessellation language (STL) files. A laboratory scanner (E4) was used for the reference scan. The exported images were analyzed with an image analysis software program (Geomagic Control X). Root-mean-square deviation (RMSD) values between the intraoral scans and the reference scan were calculated to assess trueness. RMSD values between each intraoral scan were calculated to assess precision. Three-way analysis of variance (ANOVA) was used to evaluate the influence of each variable, and Tukey HSD tests were used for multiple comparisons (α=.05). RESULTS: For trueness evaluation, tip size was the only significant factor (P<.001). The scans made with a smaller tip showed lower trueness than the scans made with a regular tip. For precision evaluation, all 3 variables, tip size, scanning speed, and scanning pattern, had significant influence (P≤.001). The use of a small tip, fast scanning speed, and S-shaped scanning pattern made intraoral scanning less precise. CONCLUSIONS: The use of a small scanner tip negatively affected both trueness and precision. Fast scanning speed and S-shaped scanning pattern produced scans with lower precision than regular or slow scanning speed and the occlusal-first scanning pattern.

Lymphocytosis and chronic lymphocytic leukaemia: investigation and management.

Lymphocytosis is a common blood-test finding. Establishing whether the cause of lymphocytosis is benign or malignant is key to managing patients appropriately. A lymphocytosis should always prompt clinical review including a thorough history, examination and appropriate preliminary investigations (blood tests, blood film). The majority of patients with chronic lymphocytic leukaemia (CLL) present incidentally due to a lymphocytosis found on routine blood tests. Patient outcomes vary considerably based on genetic pre-disposition and various prognostic markers (age, Binet or Rai staging, and B2-microglobulin). Although not curative, chemo-immunotherapy is an effective treatment strategy for the majority of CLL patients with progressive disease. More recently, novel oral therapies have been developed that target key signalling and apoptosis pathways and that are being used in relapse settings and as first-line treatments for certain patients.

Acute leukaemia: no reason to panic.

Acute leukaemia is characterised by uncontrolled expansion of immature leukocytes, either myeloid or lymphoid progenitors, leading to acute myeloid leukaemia (AML) and acute lymphoid leukaemia (ALL), respectively. If left untreated, it is life-threatening and can lead to death within weeks. When acute leukaemia is suspected, urgent haematology input should be sought. Appropriate investigations are needed promptly to confirm diagnosis and start treatment. A multidisciplinary approach is vital to ensure appropriate management.

Elucidation of Focal Adhesion Kinase as a Modulator of Migration and Invasion and as a Potential Therapeutic Target in Chronic Lymphocytic Leukemia.

The retention and re-migration of Chronic Lymphocytic Leukemia cells into cytoprotective and proliferative lymphoid niches is thought to contribute to the development of resistance, leading to subsequent disease relapse. The aim of this study was to elucidate the molecular processes that govern CLL cell migration to elicit a more complete inhibition of tumor cell migration. We compared the phenotypic and transcriptional changes induced in CLL cells using two distinct models designed to recapitulate the peripheral circulation, CLL cell migration across an endothelial barrier, and the lymph node interaction between CLL cells and activated T cells. Initially, CLL cells were co-cultured with CD40L-expressing fibroblasts and exhibited an activated B-cell phenotype, and their transcriptional signatures demonstrated the upregulation of pro-survival and anti-apoptotic genes and overrepresentation of the NF-κB signaling pathway. Using our dynamic circulating model, we were able to study the transcriptomics and miRNomics associated with CLL migration. More than 3000 genes were altered when CLL cells underwent transendothelial migration, with an overrepresentation of adhesion and cell migration gene sets. From this analysis, an upregulation of the FAK signaling pathway was observed. Importantly, PTK2 (FAK) gene expression was significantly upregulated in migrating CLL cells (PTK2 Fold-change = 4.9). Here we demonstrate that TLR9 agonism increased levels of p-FAK (p ≤ 0.05), which could be prevented by pharmacological inhibition of FAK with defactinib (p ≤ 0.01). Furthermore, a reduction in CLL cell migration and invasion was observed when FAK was inhibited (p ≤ 0.0001), supporting a role for FAK in both CLL migration and tissue invasion. When taken together, our data highlights the potential for combining FAK inhibition with current targeted therapies as a more effective treatment regime for CLL.

Targeting the Non-Canonical NF-κB Pathway in Chronic Lymphocytic Leukemia and Multiple Myeloma.

In this study, we evaluated an NF-κB inducing kinase (NIK) inhibitor, CW15337, in primary chronic lymphocytic leukemia (CLL) cells, CLL and multiple myeloma (MM) cell lines and normal B- and T-lymphocytes. Basal NF-κB subunit activity was characterized using an enzyme linked immunosorbent assay (ELISA), and the effects of NIK inhibition were then assessed in terms of cytotoxicity and the expression of nuclear NF-κB subunits following monoculture and co-culture with CD40L-expressing fibroblasts, as a model of the lymphoid niche. CW15337 induced a dose-dependent increase in apoptosis, and nuclear expression of the non-canonical NF-κB subunit, p52, was correlated with sensitivity to CW15337 (p = 0.01; r2 = 0.39). Co-culture on CD40L-expressing cells induced both canonical and non-canonical subunit expression in nuclear extracts, which promoted in vitro resistance against fludarabine and ABT-199 (venetoclax) but not CW15337. Furthermore, the combination of CW15337 with fludarabine or ABT-199 showed cytotoxic synergy. Mechanistically, CW15337 caused the selective inhibition of non-canonical NF-κB subunits and the transcriptional repression of BCL2L1, BCL2A1 and MCL1 gene transcription. Taken together, these data suggest that the NIK inhibitor, CW15337, exerts its effects via suppression of the non-canonical NF-κB signaling pathway, which reverses BCL2 family-mediated resistance in the context of CD40L stimulation.

Extraocular Muscle Volumetry for Assessment of Thyroid Eye Disease.

BACKGROUND: In this study we evaluate the diagnostic accuracy of extraocular muscle volumetry in detecting thyroid eye disease and to compare the results with simple measurements of maximal medial rectus (MR) diameter. METHODS: Cross-sectional study that included 47 eyes of 47 patients with thyroid eye disease and 47 healthy controls. Patients underwent slitlamp examination and imaging consisting of computed tomography scans. Image segmentation and volume measurements were performed by 2 independent researchers. Intraobserver and interobserver reliability testing was also conducted. RESULTS: Total extraocular muscle volume was 7.31 ± 1.88 cm3 and medial volume was 2.38 ± 0.73 cm3 in the study group. In this group, the maximum measured diameter of the MR was 6.67 ± 0.35 mm. MR volume was statistically associated with maximum MR diameter (r = 9.78; P < 0.001). Both MR volume and maximum MR diameter measurements showed good predictive efficacy as shown using receiver operator characteristic curve analysis. CONCLUSIONS: Complications of thyroid eye disease are often sight threatening, and timely diagnosis is crucial for the management of the entity and its sequelae. The results of this study imply that simple measurements of maximum MR diameter are sensitive enough to establish diagnosis.

The anatomical variant of high soleus muscle may predispose to tendinopathy: a preliminary MR study.

PURPOSE: This study aimed to examine the anatomic variations at the level of the distal soleus musculotendinous junction and the possible association between the length of the free tendon and the development of symptomatic Achilles tendinopathy. METHODS: We retrospectively assessed 72 ankle MRI studies with findings of Achilles tendinopathy (study group, 26 females/46 males, mean age 52.6 ± 10.5 years, 30 right/42 left) and 72 ankle MRI studies with normal Achilles tendon (control group, 32 females/40 males, mean age 35.7 ± 13.7 years, 42 right/30 left side). We measured the distance from the lowest outline of the soleus myotendinous junction to the proximal outline of the Achilles tendon insertion (length of the free tendon, diameter a) and to the distal outline of the insertion (distance B). We also measured the maximum thickness of the free tendon (diameter c) and the distance between the levels of maximum thickness to the proximal outline of the Achilles tendon insertion (distance D). All measurements were assessed twice. Statistical analysis was performed using independent t test. RESULTS: Distances A and B were significantly larger in tendinopathic tendons (59.7 and 83.4 mm, respectively) than normal Achilles tendons (38.5 and 60.8 mm, respectively) (p = 0.001). Mean distance C was larger in tendinopathic than normal tendons (11.2 versus 4.9 mm). Distances C and D were significantly larger in males than females. There was no significant difference in the measurements between sides. CONCLUSION: There is wide anatomical variation in the length of the free Achilles tendon. Tendinopathy may be associated with the thicker free part of the Achilles tendon. The anatomical variant of the high soleus musculotendinous junction resulting in a longer free Achilles tendon may be a predisposing factor to the development of tendinopathy.

Changes in peri-ocular anatomy and physiology in pseudoexfoliation syndrome (Review).

Pseudoexfoliation syndrome (PEX) is characterized by the deposition of proteinaceous material in the anterior ocular segment (resulting in ophthalmic pathologies such as glaucoma and increased risk of complications in cataract surgery), but also by several systemic manifestations. The involvement of peri-ocular tissues in PEX, including the eyelid skin, lacrimal gland, conjunctiva, orbital fat and vessels, as well as the optic nerve, has been reported by several previous studies. The peri-ocular effects of PEX include the development of eyelid laxity, conjunctival chalasis, tear film abnormalities, pronounced orbital fat atrophy in response to the administration of prostaglandin analogues in pseudoexfoliative glaucoma, deficient orbital vascular supply and biomechanical changes in both the eyeball and the optic nerve. These effects may have important clinical implications, including increased difficulty in cataract surgery, ocular surface disease and eyelid margin malpositions.

Anatomical variations and interconnections of the superior peroneal retinaculum to adjacent lateral ankle structures: a preliminary imaging anatomy study.

AIM: This imaging anatomy study aimed at detecting anatomical variations and potential interconnections of the superior peroneal retinaculum to other lateral stabilizing structures. MATERIALS AND METHODS: We retrospectively reviewed the imaging archives of 63 patients (38 females, 25 males, mean age 32.7, range 18-58 years) with available ankle US, MR and CT images to detect whether US and MR can detect the presence of interconnections between the superior peroneal retinaculum and the anterior talofibular ligament, inferior extensor retinaculum and peroneal tendon sheath. We evaluated the presence of common anatomical variations including low peroneus brevis muscle belly, peroneal tubercle, os peroneum, and retromalleolar fibular groove shape in relation to the presence of superior peroneal retinaculum connections. RESULTS: The connections of the superior peroneal retinaculum can be revealed on magnetic resonance imaging (MRI) and ultrasound (US). The connection to the anterior talofibular ligament was located (a) inferior to the lateral malleolus, (b) at the level of the lateral malleolus and (c) on both levels, respectively (a) 49.2% on MRI and 39.7% on US, p <0.05, (b) 44.4% and 58.7%, p <0.05, 36.5% and (c) 27%, p <0.05. Superior peroneal retinaculum-inferior extensor retinaculum (MRI 47.6%, US 28.6% p <0.001) and superior peroneal retinaculum-peroneal tendon sheath (MRI 22.2%, US 25.4% p >0.05) connections were also found both on MR and US. CONCLUSION: Ankle US and MR revealed interconnections between the superior peroneal retinaculum and the anterior talofibular ligament, inferior extensor retinaculum, and superior peroneal retinaculum. Our results are a starting point for further studies on the connections of the superior peroneal retinaculum and the applicability of ultrasound and MRI in assessing their occurrence. Knowledge of the anatomical connections of the superior peroneal retinaculum may help radiologists with the assessment of lateral ankle injuries, and surgeons with treatment planning.

Using techno-economic modelling to determine the minimum cost possible for a microbial palm oil substitute.

BACKGROUND: Heterotrophic single-cell oils (SCOs) are one potential replacement to lipid-derived biofuels sourced from first-generation crops such as palm oil. However, despite a large experimental research effort in this area, there are only a handful of techno-economic modelling publications. As such, there is little understanding of whether SCOs are, or could ever be, a potential competitive replacement. To help address this question, we designed a detailed model that coupled a hypothetical heterotroph (using the very best possible biological lipid production) with the largest and most efficient chemical plant design possible. RESULTS: Our base case gave a lipid selling price of $1.81/kg for ~ 8,000 tonnes/year production, that could be reduced to $1.20/kg on increasing production to ~ 48,000 tonnes of lipid a year. A range of scenarios to further reduce this cost were then assessed, including using a thermotolerant strain (reducing the cost from $1.20 to $1.15/kg), zero-cost electricity ($ 1.12/kg), using non-sterile conditions ($1.19/kg), wet extraction of lipids ($1.16/kg), continuous production of extracellular lipid ($0.99/kg) and selling the whole yeast cell, including recovering value for the protein and carbohydrate ($0.81/kg). If co-products were produced alongside the lipid then the price could be effectively reduced to $0, depending on the amount of carbon funnelled away from lipid production, as long as the co-product could be sold in excess of $1/kg. CONCLUSIONS: The model presented here represents an ideal case that which while not achievable in reality, importantly would not be able to be improved on, irrespective of the scientific advances in this area. From the scenarios explored, it is possible to produce lower cost SCOs, but research must start to be applied in three key areas, firstly designing products where the whole cell is used. Secondly, further work on the product systems that produce lipids extracellularly in a continuous processing methodology or finally that create an effective biorefinery designed to produce a low molecular weight, bulk chemical, alongside the lipid. All other research areas will only ever give incremental gains rather than leading towards an economically competitive, sustainable, microbial oil.

Ultrasound Elastography in Ocular and Periocular Tissues: A Review.

Ultrasound elastography has become available in everyday practice, allowing direct measurement of tissue elasticity with important and expanding clinical applications. Several studies that have evaluated pathological and non-pathological tissues have demonstrated that ultrasound elastography can actually improve the diagnostic accuracy of the underlying disease process by detecting differences in their elasticity. Ocular and periocular tissues can also be characterized by their elastic properties. In this context, a comprehensive review of literature on ultrasound elastography as well as its current applications in Ophthalmology is presented.