Spontaneous Spinal Cord Herniation with Post-operative paraplegia- A case report with 10-year follow-upAbstract:Background: Spinal cord herniation is an uncommon diagnosis in the field of spine surgery. The usual presentation of spontaneous spinal cord herniation is in the form of progressive Brown-Sequard syndrome. We describe a case of a 37-year-old male with progressive back pain and sensory deficits due to spinal cord herniation and a post-operative complication associated with reduction of the hernia.Case description: A 37-year-old male presented with insidious onset upper back pain and altered sensations of pain and temperature over the right half of the body below the nipple 2 months before the examination. The patient did not have motor weakness of lower limbs, abnormal/ involuntary movements, or loss of control over the bowel and bladder. MRI of the thoracic spine showed an anterolateral defect(left) at the level of the T2-T3 vertebra. A posterior approach was chosen and the cord with roots was reduced into the dura. The defect was covered by a dural graft (Lyodura) and the wound was closed with a drain insitu. On the 3rd post-operative day, patient developed paraplegia. Patient was treated by exploration and decompression of the hematoma that compressed spinal cord. The deficits were completely recovered at one-month follow-up.Conclusion: Patients with spinal cord herniation and neurologic deficits when treated timely with reduction of the hernia, have good outcomes. The drain should be removed only when the treating team is satisfied regarding the lack of ongoing hemorrhage. The recovery was maintained till the last follow-up at 10 years.Key words: spontaneous spinal cord herniation, spinal cord defect, paraplegia, Brown-Sequard syndrome

INTRODUCTIONAn unpleasant experience for both the patient and the anesthetist, post-dural puncture headache (PDPH) is a complication of spinal anesthesia or lumbar puncture. It is believed to be caused by cerebral vasodilation, which is an indirect consequence of low cerebrospinal fluid (CSF) pressure, or meningeal traction linked to low CSF pressure.1 PDPH incidence varies, although it is generally thought to be 36% or more after lumbar puncture, 0%-10% after spinal anesthesia, and 81% after an unintentional dural puncture during epidural insertion.2, 3 Although PDPH typically resolves on its own, it can make it difficult for mothers to care for their infants and lengthen hospital stays. Serious side effects such as subdural hematoma, convulsions, sagittal sinus thrombosis, and cranial nerve palsies are more infrequently linked to PDPH.

1. Over the last four decades coral disease research has continued to provide reports of disease states, the occurrence and severity of disease outbreaks, and associated disease signs however nomenclature and protocols for microscopic disease descriptions have yet to be implemented. Histopathology using systematic protocols is a gold standard for the microscopic assessment of diseases in veterinary and medical research. Increasing disease outbreaks on coral reefs as human impacts intensify highlights the need to also establish standardised diagnostic terminology and methodology for coral disease research. 2. Here we apply a systematic approach to collating, reviewing, and evaluating histopathological methods used to study white diseases in hard coral taxa and map research effort in this field spanning study design, sample processing and analysis in the 33 publications identified between 1984 and 2022. 3. We find that studies to-date have not uniformly detailed methodologies, and terminology associated with histopathological reporting and disease description is inconsistent between studies. Combined these limitations reduce study repeatability, limiting the uptake of histopathology in coral disease research and the capacity for researchers to compare disease reports. 4. A primary outcome of this study is revision of the most widely used terminology applied to coral tissue and development of recommendations for standardised reporting procedures with the aim of increasing accessibility and uptake of histopathology in addition to allowing for ongoing comparative analysis through living systematic reviews for the coral disease field.

Background and Objectives: Initially developed as immunosuppressive agents, mTOR inhibitors are currently used widely in the management of vascular malformations and tumors. The incidence of infectious complications in the vascular anomalies (VA) population is not well defined. The goal of this systematic review was to better define the types and severity of reported infectious complications in patients with VAs treated with mTOR inhibition. Methods: This was a systematic review conducted following PRISMA guidelines evaluating all research articles focused on infectious complications in patients with VAs treated with sirolimus or everolimus. Thirty articles including 1181 total patients and 315 infections (in 290 unique patients) were ultimately included. Results: The majority of infections were viral upper respiratory (n=137, 54%), followed by pneumonia (n=52, 20%), and cutaneous infections (n=20, 8%). There were 6 total infection-related fatalities, which all occurred in patients younger than 2 years. Only 1 case of Pneumocystis jirovecii pneumonia (PJP) was reported. This was in an infant with KHE who was also treated with steroids and did not receive PJP prophylaxis. Almost 1/3 (n=95, 32%) of infectious complications were graded 3 to 4 according to CTCAE criteria. Details of patient age, subtype of VA, and timing of infection were lacking from many reports. Conclusions: Most infectious complications reported in patients with VA on mTOR inhibitors were viral respiratory infections and non-severe. Bacteremia, infectious fatalities, and PJP are exceedingly rare. Future studies are needed to clarify the spectrum of infectious risks in VA patients and to provide guidance for infection prevention.

While the survival of children with cancer has improved over time, infection remains a major morbidity and mortality risk. We conducted a systematic literature review to determine the unmet needs in diagnosing infection in immunocompromised children with cancer. The comprehensive search strategy followed the guidelines established by the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 statement and spanned multiple bibliographic databases and other public sources from January 1, 2012–June 23, 2022. From 5,188 records, 34 unique pediatric-focused studies met inclusion criteria. This review highlights the lack of published data on infectious disease testing in pediatric oncology patients and the need for well-designed clinical impact and cost-effectiveness studies of both existing and novel diagnostic platforms. Such studies are necessary to optimize diagnostic and antimicrobial stewardship, leading to improvement in patient outcomes.

α-Olefins as aliphatic terminal alkenes could be obtained easily from numerous contemporary synthetic reactions as well as petrochemical industry, and also found in natural products. Compared to the alkenes attaching the directing groups or activating group, the catalytic asymmetric reaction of unactivated terminal alkenes presents great challenges due to the weak electron effect and small steric hindrance effect. This review mainly summerizes the latest progress of the asymmetric reaction of unactivated terminal olefins since 2016.

[The Instructions to Authors state no abstract is required for a Research Letter but the submission sysem demands one, so this text is included.] In order to assess whether measuring HE4 might add to the performance of CA125 in diagnosing ovarian cancer, we measured both markers in 33 individuals with elevated CA125. We found that HE4 elevated above 150 pmol/l was present in all 9 cases of ovarian cancer and in the single case of pancreatic cancer.  HE4 levels below 77pmol/l seen in 16 cases were associated with non-malignant gynaecological conditions and with there being no identified cause for elevated CA125. Two cases with HE4 between 77 and 149 pmol/l had no gynaecological conditions and 2 had no an identifiable cause.  Measuring both markers could lead to improved sensitivity and specificity of the initial diagnostic step.

Scientific outreach activities play an important role in disseminating knowledge, connecting the general public to research and breaking down scientific scepticism barriers. However, the vision impaired community is often disadvantaged when the most common audio-visual approach of scientific communication is applied. Here we integrated tactile clues in the scientific communication of immune processes involved in the autoimmune skin disease psoriasis. We encouraged participation of the vision impaired community by engagement with tactile scientific origami art, a haptic poster and wood carved molecular models. Readily accessible science communication that engages a number of senses is a critical step towards making science more inclusive, and engaging for individuals with a wide range of sensory abilities. The Sensory Science approach aligns with the principles of equity, diversity, and inclusion and helps create a more informed and scientifically literate public.

Objective Machine learning has been effective in other areas of medicine, this study aims to investigate this with regards to HNC and identify which algorithm works best to classify malignant patients. Design An observational cohort study. Setting Queen Elizabeth University Hospital. Participants Patients who were referred via the USOC pathway between January 2019 and May 2021. Main outcome measures Predicting the diagnosis of patients from three categories, benign, potential malignant and malignant, using demographics and symptoms data. Results The logistic regression-based models with a penalty term worked best on the data, ridge achieving an AUC of 0.7081. The demographic features describing living alone and recreational drug use history were the most important variables alongside the red flag symptom of a neck lump. Conclusion Further studies should aim to collect larger samples of malignant and pre-malignant patients to improve the class imbalance and increase the performance of the machine learning models.

A straightforward electrochemical hydrogenation of benzo[b]thiophene 1,1-dioxides with HFIP as the hydrogen donor has been re-ported in an undivided cell under metal-free conditions. Moreover, the tolerance of various functional groups and scaled-up experi-ments showed the practicability and potential applications of this methodology.

Simulation and optimization of chemical flowsheets rely on the solution of a large number of non-linear equations. Finding such solutions can be supported by constructing machine-learning based surrogates, relating features and outputs by simple, explicit functions. In order to generate training data for those surrogates computationally efficiently, schemes to adaptively sample the feature space are mandatory. In this article, we present a novel family of utility functions to favor an adaptive, Bayesian exploration of the feature space in order to identify regions that are convergent, fulfill customized inequality constraints and are Pareto-optimal with respect to conflicting objectives. The benefit is illustrated by small toy-examples as well as by industrially relevant chemical flowsheets.

We report on the spectroscopic investigation of common bacteria encountered in biopharmaceutical industries with spectroscopic definition and specificity using mid-infrared laser spectroscopy. This study describes the detection of three different bacteria species using quantum cascade laser spectroscopy coupled to a grazing angle probe (QCL-GAP). Stainless steel substrates were used as support for the bacterial samples. QCL-GAP spectroscopy was assisted by multivariate analysis (MVA) to assemble a powerful spectroscopic technique with classification, identification, and quantification resources. The bacterial species analyzed, Staphylococcus aureus, Staphylococcus epidermidis, and Micrococcus luteus, were used to challenge the technique’s capability to discriminate microorganisms from the same family. Principal component analysis and partial least squares-discriminant analysis differentiated between the bacterial species using QCL-GAP. Spectral differences in the bacterial membrane were used to determine if these microorganisms were present in the samples analyzed. Results herein provided effective discrimination for the bacteria under study with high sensitivity and specificity values.

Alemtuzumab‐induced petechiae and epistaxis in a patient with relapsing remitting multiple sclerosis; A case report Farhad Mahmoudi1*, Sayed Ali Emami1, Farid Masaeli1, Najmeh Rayatpisheh21 School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran2School of Medicine, Shahrekord University of Medical Sciences, Shahrekord, IranCorresponding author*Farhad MahmoudiSchool of Medicine,Isfahan University of Medical Sciences,Isfahan, IranEmail: [email protected]: This case report presents a 58-year-old woman with Multiple Sclerosis (MS) who developed petechiae and epistaxis, rare side effects following Alemtuzumab treatment. While these reactions are infrequent, heightened awareness among healthcare providers is essential as Alemtuzumab gains popularity in MS treatment. Recognizing and managing such hypersensitivity reactions promptly is crucial for improved patient care. 1.Introduction Multiple Sclerosis (MS) is an autoimmune disease that affects the central nervous system. The course of the disease varies among individuals, leading to a wide range of symptoms and patterns of presentation. Additionally, there are other conditions, such as radiologically isolated syndrome, which can progress to MS(1). While there is no curative therapy for this condition, certain drugs can modify the course of the disease and improve the prognosis and quality of life for patients.Disease-modifying treatments (DMTs) are the preferred treatment option for patients with MS. Alemtuzumab is an intravenously administered DMT drug that has been available since 2014 for the treatment of patients with multiple sclerosis who have not responded adequately to two or more DMTs. It is a recombinant DNA-derived humanized monoclonal antibody that selectively binds to the CD52 antigen on B and T lymphocytes, depleting them from the bloodstream. This drug has been described as a safe and effective treatment with minimal side effects for patients with relapsing-remitting multiple sclerosis.(2)While there are few studies on the cutaneous adverse effects of Alemtuzumab, in this study, we report the first case of an MS patient treated with Alemtuzumab who developed drug-induced petechiae and epistaxis.2. Case presentationA 58-year-old Caucasian woman with relapsing-remitting multiple sclerosis, who had no previous medical conditions, presented to the emergency department due to muscle spasms and stiffness in her right foot. Neurological examination revealed weakness in her right lower limb with 3/5 muscle strength. She was diagnosed with MS at the age of 26 through an MRI and had previously been on weekly Interferon-beta (IFNb) treatment. During acute MS attacks, she received intravenous corticosteroids. Despite being on disease-modifying therapies (DMTs), she experienced more relapses in the last year, and her Expanded Disability Status Scale (EDSS) was 3. During the current hospitalization, the patient underwent brain and cervical spinal MRI, which revealed the appearance of new periventricular white active plaques in addition to previous black old lesions.Considering the progression of her disease condition, she was started on treatment with Alemtuzumab at a dose of 12mg/day IV. There were no drug reactions, and after completing the treatment, her muscle spasms and stiffness resolved, and the patient was discharged from the hospital.The day after, the patient came to the hospital to receive the second dose of the drug. While receiving the treatment, her condition remained stable, and she did not experience any notable symptoms. However, one day after finishing the first dose, the patient started to experience a gradual appearance of petechiae on her upper and lower limbs, chest, shoulders, and back. Moreover, a few minutes later, she developed epistaxis. Her blood pressure and heart rate were 127/73 and 87, respectively. The patient denied any previous history of eczema, skin issues, or respiratory allergies.Dermatology was consulted to investigate the possible causes of petechiae, and ENT was consulted to manage and evaluate the epistaxis. Despite applying pressure to the nostrils and placing ice on the forehead, the epistaxis did not cease. Consequently, the patient underwent posterior nasal packing, which successfully halted the bleeding.

Millions of people suffer from dopamine-related disorders spanning disturbances in movement, cognition and emotion, often attributed to changes in striatal dopamine function. Understanding how dopamine signaling in the striatum and basal ganglia shapes human behavior is fundamental to advancing the treatment of affected patients. Dopaminergic neurons innervate large scale brain networks and many different roles for dopamine signals have been proposed, such as invigoration of movement and tracking of reward contingencies. The canonical circuit architecture of cortico-striatal loops sparks the question, whether dopamine signals in the basal ganglia serve an overarching computational principle which could provide new insights into symptom generation in psychiatry to neurology. Here, we review the perspective that dopamine could bidirectionally control neural population dynamics, increasing, or decreasing their strength and likelihood to reoccur in the future, a process previously termed neural reinforcement. We outline how the basal ganglia pathways could drive strengthening and weakening of circuit dynamics and discuss the implication of this hypothesis on the understanding of motor signs of Parkinson’s disease (PD), the most frequent dopaminergic disorder. We propose that loss of dopamine in PD may lead to a pathological brain state where repetition of neural activity leads to weakening and instability, possibly explanatory for the fact that movement in PD deteriorates with repetition, as defined by the sequence effect or decrement of movement. Finally, we speculate on how therapeutic interventions such as deep brain stimulation (DBS) may be able to reinstate reinforcement signals and thereby improve treatment strategies of PD in the future.

In this study, hesperetin was shown to inhibit the replication of multiple poxviruses, including buffalopox virus (BPXV), vaccinia virus, and lumpy skin disease virus (LSDV). Hesperetin mainly suppressed viral protein synthesis without affecting other steps of the viral life cycle such as attachment, entry, and budding. In a chromatin immunoprecipitation (CHIP) assay, we further demonstrated that hesperetin-induced reduction in BPXV protein synthesis is due to disruption of the binding of the 5’ cap of viral mRNA with the cellular translation initiation factor eIF4E. The molecular docking and MD simulation studies, also confirmed binding of the hesperetin with the cap-binding pocket of eIF4E, in a similar conformation as m7GTP binds. In a BPXV egg infection model, hesperetin was shown to suppress the development of pock lesions on the chorioallantoic membrane, as well as the associated mortality of the chicken embryos. Most importantly, long-term culture of BPXV in the presence of hesperetin did not induce the generation of drug-resistant viral mutants. In conclusion, we for the first time demonstrated the antiviral activity of hesperetin against poxviruses, besides providing novel mechanistic insights into the antiviral action of hesperetin.

Background: Intracardiac echocardiography (ICE) is increasingly used during left atrial appendage occlusion (LAAO) as an alternative to transesophageal echocardiography (TEE) Aim: To evaluate the impact of ICE vs. TEE guidance during LAAO on procedural characteristics and acute outcomes, as well the presence of peri-device leaks and residual septal defects during follow-up. Methods: All studies comparing ICE-guided vs. TEE-guided LAAO were identified. The primary outcomes were procedural efficacy and occurrence of procedure-related complications. Secondary outcomes included lab efficiency (defined as a reduction in in-room time), procedural time, fluoroscopy time, and presence of peri-device leaks and residual interatrial septal defects (IASD) during follow-up. Results: Twelve studies (n=5637) were included. There were no differences in procedural success group (98.3% vs. 97.8%; OR 0.73, 95% CI 0.42-1.27, p=0.27; I2=0%) or adverse events (4.5% vs. 4.4%; OR 0.81 95% CI 0.56-1.16, p=0.25; I2=0%) between the ICE-guided and TEE-guided groups. ICE guidance reduced in in-room time (mean-weighted 28.6-minute reduction in in-room time) without differences in procedural time or fluoroscopy time. There were no differences in peri-device leak (OR 0.93, 95% CI 0.68-1.27, p=0.64); however, an increased prevalence of residual IASD was observed with ICE-guided vs. TEE-guided LAAO (46.3% vs. 34.2%; OR 2.23, 95% CI 1.05-4.75, p=0.04). Conclusion: ICE guidance is associated with similar procedural efficacy and safety, but could result in improved lab efficiency (as established by a significant reduction in in-room time). No differences in the rate of periprocedural leaks were found. A higher prevalence of residual interatrial septal defects was observed with ICE guidance.

Paediatric home invasive mechanical ventilation patients are a small but resource intensive cohort, requiring close monitoring and multidisciplinary care. Patients are often dependent on their ventilator for life support, with any significant complications such as equipment failure, tracheostomy blockage, or accidental decannulation becoming potentially life threatening, if not identified quickly. This review discusses the indications and variations in practice worldwide, in terms of models of care, including home care provision, choice of equipment and monitoring. With advances in technology, optimal monitoring strategies for home, continue to be debated: In-built ventilator alarms are often inadequately sensitive for paediatric patients, necessitating additional external monitoring devices to minimise risk. Pulse oximetry has been the preferred monitoring modality at home, though in some special circumstances such as congenital central hypoventilation syndrome, home carbon dioxide monitoring may be important to consider. Children should be under regular follow up at specialist respiratory centres where clinical evaluation, nocturnal oximetry and capnography monitoring and/or poly(somno)graphy and analysis of ventilator download data can be performed regularly to monitor progress. Recent exciting advances in technology, particularly in telemonitoring, which have potential to hugely benefit this complex group of patients are also discussed.

Substance use disorders (SUDs) are highly prevalent and have deleterious effects on one’s health and well-being. Inpatient treatment for SUDs reduces patient relapse, which subsequently ameliorates these negative effects on the individual and society. Additionally, those who complete treatment are less likely to relapse compared to those who do not complete treatment. Thus, maintaining patient engagement in treatment and reducing the rates of those leaving against medical advice (AMA) is particularly important. Examining the factors and comorbidities that may contribute to treatment dropout has the potential to identify at-risk patients in need of additional individualized intervention. The current study aimed to examine comorbid anxiety, depression, and post-traumatic stress disorder (PTSD) symptoms as predictors of dropout AMA in a residential substance use treatment population. Results showed that patients with social anxiety were more likely to leave treatment AMA, while those with PTSD were more likely to complete treatment. Findings suggest that PTSD-specific treatment, as offered in this facility, may help with patient retention, while group focused therapy may be distressing to those with social anxiety. Clinical implications of this research may include incorporating evidence-based practice for social anxiety early during inpatient treatment to reduce anxiety such that patients may better engage with SUDs treatment.