Deepti Negi, Penelope M. Tsimbouri, Matthew J. Dalby
et al.
Bone is a dynamic tissue with ecological and evolutionary importance, as it can grow and remodel itself in response to mechanical stimuli. In mammals, osteocytes are widely recognised as the central regulators of bone formation and mechanotransduction. However, many advanced teleosts lack these cells yet still exhibit evidence of bone formation and remodelling. This challenges the prevailing view that osteocytes are indispensable for these processes. Notably, these anosteocytic teleosts exhibit clear responses to mechanical loading, suggesting alternative mechanisms at play. African cichlids, known for their remarkable ecological diversification, which occurs in craniofacial bone morphology. However, these differences are based on very few genetic changes, while including interspecific variation in bone remodeling capacities. Thus, cichlid, being anosteocytic, and variable in remodeling abilities based on very few genetic changes, represents an ideal model system for understanding the mechanisms underlying remodeling. This protocol outlines the development of primary cell cultures from cichlid jaw bones that can be applied across species, establishing a foundation for future research aimed at elucidating the cellular and molecular mechanisms underlying bone formation and remodelling in anosteocytic systems.
IntroductionHead and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous malignancy with poor overall prognosis. Recent studies have suggested that propionate metabolism-related genes (PMRGs) may play key roles in tumor progression and immune regulation, yet their functions in HNSCC remain unclear.MethodsTranscriptomic data from 502 HNSCC tumor samples and 44 normal tissue samples were obtained from the UCSC Xena database as the training set. Two independent datasets (GSE41613 and GSE6631) from the GEO database were used for validation. Differentially expressed genes (DEGs), key module genes identified via weighted gene co-expression network analysis (WGCNA), and PMRGs were intersected to identify candidate genes. A prognostic model was constructed using Cox regression and LASSO analysis. Immune infiltration, somatic mutations, and drug sensitivity were compared between high- and low-risk groups. Gene expression was further validated by RT-qPCR using clinical samples.ResultsA total of 42 intersecting genes were identified, and four feature genes (PRKAA2, SLC7A5, GRIP2, CHGB) were selected to build the prognostic model. The model effectively stratified patients into high- and low-risk groups with significant survival differences in both the training and validation cohorts. The high-risk group exhibited marked differences in immune cell infiltration, immune checkpoint expression, and cancer immune cycle activity. Mutation burden and drug sensitivity also varied significantly between risk groups. A nomogram combining risk score and pathological N stage showed strong predictive performance.DiscussionThis study highlights the potential role of PMRGs in immune regulation and tumor progression in HNSCC. The proposed four-gene signature provides a novel tool for prognosis prediction and offers new insights for risk stratification and individualized therapy. Further multicenter validation and mechanistic studies are warranted.
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Vincenzo Marcelli, Vincenzo Marcelli, Beatrice Giannoni
et al.
Downbeat nystagmus (DBN) is a neuro-otological finding frequently encountered by clinicians dealing with patients with vertigo. Since DBN is a finding that should be understood because of central vestibular dysfunction, it is necessary to know how to frame it promptly to suggest the correct diagnostic-therapeutic pathway to the patient. As knowledge of its pathophysiology has progressed, the importance of this clinical sign has been increasingly understood. At the same time, clinical diagnostic knowledge has increased, and it has been recognized that this sign may occur sporadically or in association with others within defined clinical syndromes. Thus, in many cases, different therapeutic solutions have become possible. In our work, we have attempted to systematize current knowledge about the origin of this finding, the clinical presentation and current treatment options, to provide an overview that can be used at different levels, from the general practitioner to the specialist neurologist or neurotologist.
Synovial sarcoma (SS) is a malignant mesenchymal neoplasm that is relatively common in the distal extremities. Primary SS of bone is an extremely rare finding. Here in this report, we present a 44-year-old male patient referred with bone and later bone fracture that was finally diagnosed with primary SS of thumerus. So far, 13 documented cases of primary SS of the bone have been reported. The current case is the second known case of primary SS of humerus. Our case was treated with both neoadjuvant and adjuvant chemotherapies associated with surgical tumor removal and prosthesis implantation. Follow-up of the case demonstrated significant remission but with late metastasis and subsequent advanced chemotherapy regimens.
Introduction
Older adults with schizophrenia often have multiple chronic conditions, or multimorbidity, yet most prior research has focused on single medical conditions.
Objectives
To characterize multimorbidity patterns and utilization among older adults with schizophrenia to understand how multimorbidity affects this population and their clinical service needs.
Methods
This retrospective cohort study included veterans aged 50 years and older with schizophrenia and followed their comorbid diagnoses and utilization (outpatient, inpatient, and emergency) from 2012 to 2019. Comorbid diagnoses included myocardial infarction, congestive heart failure, stroke, chronic obstructive pulmonary disease (COPD), cancer, dementia, traumatic brain injury, hepatitis C, osteoarthritis, renal disease, chronic pain, sleep disorder, depression, dysthymia, posttraumatic stress disorder (PTSD), general anxiety disorder, alcohol use disorder, other substance use disorder, and tobacco use disorder. Latent class analysis was used to identify latent profiles of psychiatric and medical comorbidity. Chi-square and F-tests were used to assess differences in demographics, comorbidities, and utilization across the latent classes.
Results
The cohort included 82,495 adults with schizophrenia. Three distinct multimorbidity classes were identified: Minimal Comorbidity (67.0% of the cohort), High Comorbidity (17.6%) and Substance Use Disorders and Related Conditions (SUDRC) (15.4%). The Minimal Comorbidity class had <10% prevalence of all comorbid diagnoses. The High Comorbidity class had >20% prevalence of congestive heart failure, COPD, dementia, renal disease, sleep disorder, and depression. The SUDRC class had >70% prevalence of alcohol and drug use disorders and >20% prevalence of COPD, hepatitis C, depression, and PTSD. Although the High Comorbidity class had the highest rates of chronic medical conditions, the SUDRC class had the highest rates of emergency and inpatient medical care and emergency, inpatient, and outpatient mental health care utilization. Comparing across classes, all p-values were <.001 for utilization.
Conclusions
Older adults with schizophrenia are a heterogeneous group with distinct multimorbidity classes and different patterns of utilization. Those with high prevalence of substance use disorders had the highest rates of emergency and inpatient medical and overall mental health care utilization. Tailoring integrated care services to target specific clinical needs could improve outcomes for this population.
Disclosure of Interest
None Declared
Background: Direct observation is an invaluable tool for assessing clinical skills. However, it is unclear whether trainees are regularly observed on internal medicine clinical teaching units (CTUs). Methods: A web-based survey was distributed to medical students and residents completing rotations on inpatient internal medicine CTUs. Participants recorded the frequency of direct observation and observational feedback received over the past week. Results: Of the 189 survey respondents, 76% reported receiving direct observation at least once. On average, six skill-specific observations were reported by each learner, with an average of two different skills being observed. Bedside clinical decision-making and physical examination skills were observed most frequently. Feedback was least often provided after the direct observation of physical examination and communication skills. Conclusions: A quarter of trainees were not regularly observed at the internal medicine CTUs. The optimal frequency of direct observation requires further study.
Noriyuki Takahashi, Takaharu Matsuhisa, Kunihiko Takahashi
et al.
Abstract Although research in general medicine is diverse, it has not been compared with research in a different medical specialty. The study aim was to understand the characteristics of research produced at Japanese university departments of general medicine and published in English-language journals, via comparison with another academic specialty, cardiology. In this cross-sectional study, a nationwide survey of the official websites of 82 university-affiliated medical schools in Japan was conducted in April 2020 to identify the heads of general medicine departments. We then surveyed the research output of these individuals in terms of original article output and research field diversity for journals listed in the Web of Science Core Collection of journals from 2010 to 2019. A similar survey of cardiology department publications was also conducted to provide a reference for intergroup comparisons and analysis of covariance. The analysis included 128 researchers from 78 general medicine departments and 96 researchers from 81 cardiology departments. The dominant research field of general medicine was general and internal medicine; that of cardiology was cardiac/cardiovascular systems. Data stratification by research field showed that general medicine researchers published significantly more articles than researchers in cardiology, a field that contains relatively few researchers. Furthermore, a comparison of individual researchers with the same number of published articles showed that researchers in general medicine departments published across a significantly wider range of fields than those in cardiology. This is the first study to describe the research characteristics of general medicine university departments in Japan through comparison with research in a different academic specialty. General medicine researchers in Japan comprise a heterogeneous group that mainly publishes research on general and internal medicine. Some general medicine researchers take a multidisciplinary approach to research and publishing.
Gelber Rosas-Patiño, Yina Jazbleidi Puentes-Páramo, Juan Carlos Menjivar-Flores
La acidez del suelo limita la disponibilidad, la absorción y la concentración de nutrientes y el rendimiento del cultivo de cacao. El objetivo fue evaluar el efecto del pH del suelo sobre la concentración de nutrientes en hoja, cáscara y grano, para cuatro clones de cacao autocompatibles (ICS-1, CCN-51) y autoincompatibles (ICS-39, TSH-565), en el departamento del Caquetá. El diseño experimental consistió en un arreglo factorial con cuatro clones (factor A), cuatro niveles de pH y fertilidad (factor B) y cuatro repeticiones. Los resultados indican diferencias en la concentración de nutrientes por efecto del clon y tratamiento, siendo la acumulación de N, P y Mg en grano>hoja>cáscara, K en cáscara>hoja>grano, Ca, Fe, Mn, Zn y B en hoja>cáscara>grano, S en cáscara>hoja>grano y Cu en grano>cáscara>hoja. La concentración de P, Mg y S fue mayor y, a su vez, menor Mn, cuando aumentó el pH. El orden de extracción nutrimental en grano fue N>K>P>Mg>S>Ca>Fe>Mn>Zn>Cu>B. Con relación a los clones, CCN-51 presentó habilidad para la toma de nutrientes y alcanzar mayores producciones, incluso, en suelos con pH ≥ 5,5, lo que sugiere efecto de las condiciones edafoclimáticas y, por lo tanto, la necesidad de evaluar los clones para cada zona de cultivo.
Oxidative stress-mediated retinal pigment epithelium (RPE) degeneration plays a vital role in retinal degeneration with irreversible visual impairment, most notably in age-related macular degeneration (AMD), but a key pathogenic factor and the targeted medical control remain controversial and unclear. In this work, by sophisticated high-throughput sequencing and biochemistry investigations, the major pathologic processes during RPE degeneration in the sodium iodate-induced oxidative stress model has been identified to be heme oxygenase-1 (HO-1)-regulated ferroptosis, which is controlled by the Nrf2–SLC7A11–HO-1 hierarchy, through which ferrous ion accumulation and lethal oxidative stress cause RPE death and subsequently photoreceptor degeneration. By direct knockdown of HO-1 or using HO-1 inhibitor ZnPP, the specific inhibition of HO-1 overexpression has been determined to significantly block RPE ferroptosis. In mice, treatment with ZnPP effectively rescued RPE degeneration and achieved superior therapeutic effects: substantial recovery of the retinal structure and visual function. These findings highlight that targeting HO-1-mediated RPE ferroptosis could serve as an effectively retinal-protective strategy for retinal degenerative diseases prevention, including AMD.
Various modalities of treatment are available for different dental diseases, but the major drawback of these conventional drug therapies is the numerous side effects associated with their use. This has led to renewed interest in the discovery of novel anti-infective natural compounds derived from plants. Plants have been the major source of medicine since the time immemorial. Turmeric has been attributed a number of medicinal properties in the traditional system of medicine. The objective of this article is to review the efficacy of turmeric herb in maintenance of oral health, in particular, and overall health, in general. Turmeric, a rhizome of Curcuma longa, is a herb known for its medicinal properties and is a more acceptable and viable option for a common man. It has proven properties like anti-inflammatory, antioxidant, antimicrobial, hepatoprotective, immunostimulant, antiseptic, and antimutagenic. Due to these properties, it is quite useful in dentistry as well. It has a role in the treatment of periodontal diseases and oral cancers. Turmeric can also be used as a pit and fissure sealant, mouth wash, and subgingival irrigant in different preparations. It can also be used as a component in local drug delivery system in gel form.
Joe Fernando Muñoz-Cerón, Mauricio Rueda-Sánchez, Oscar Enrique Pradilla-Vesga
et al.
SUMMARY INTRODUCTION:
Chronic daily headache is a high impact entity in the general population. Although chronic migraine and tension-type headache are the most frequent conditions, it is necessary to consider hemicrania continua and new daily persistent headache as part of the differential diagnoses to perform a correct therapeutic approach.
OBJECTIVE:
To make recommendations for the treatment of chronic daily headache of primary origin
METHODOLOGY:
The Colombian Association of Neurology, by consensus and Grade methodology (Grading of recommendations, assessment, development and evaluation), presents the recommendations for the preventive treatment of each of the entities of the daily chronic headache of primary origin group.
RESULTS:
For the treatment of chronic migraine, the Colombian Association of Neurology recommends onabotulinum toxin A, erenumab, topiramate, flunarizine, amitriptyline, and naratriptan. In chronic tension-type headache the recommended therapeutic options are amitriptyline, imipramine, venlafaxine and mirtazapine. Topiramate, melatonin, and celecoxib for the treatment of hemicrania continua. Options for new daily persistent headache include gabapentin and doxycycline. The recommendations for inpatient treatment of patients with chronic daily headache and the justifications for performing neural blockades as a therapeutic complement are also presented.
CONCLUSION:
The therapeutic recommendations for the treatment of chronic daily headache based on consensus methodology and Grade System are presented.
Angela Clapperton, Stuart Newstead, Lyndal Bugeja
et al.
Abstract Objective: This study aimed to identify stressors over‐represented in the 12 months prior to death among 553 Victorian adults who died by suicide. Methods: Age‐ and sex‐specific suicide rates and relative risks of suicide were calculated using numerator data on suicides occurring in 2013 by people with a given exposure sourced from the Victorian Suicide Register and denominator data on the total Victorian population with that exposure sourced from the 2014 Australian Bureau of Statistics General Social Survey. Results: Mental illness was associated with increased suicide risk among people of all age groups and both sexes. Alcohol and/or other drug problems were associated with increased risk for males and females of all ages, with the exceptions of the oldest males and females, and the youngest females. Trouble with the police was associated with increased risk among all but the oldest males, whereas among females it was associated with elevated risk in those aged 25–44 years and 65+ years. Conclusions and Implications for public health: Males experiencing mental illness and alcohol and other drug problems should be a particular priority for suicide prevention initiatives but people exposed to other stressors such as contact with the police and divorce/relationship separation also warrant attention.
A published study used a stochastic branching process to derive equations for the mean and variance of the probability of, and time to, extinction in population of tsetse flies (Glossina spp) as a function of adult and pupal mortality, and the probabilities that a female is inseminated by a fertile male. The original derivation was partially heuristic and provided no proofs for inductive results. We provide these proofs, together with a more compact way of reaching the same results. We also show that, while the published equations hold good for the case where tsetse produce male and female offspring in equal proportion, a different solution is required for the more general case where the probability (β) that an offspring is female lies anywhere in the interval (0, 1). We confirm previous results obtained for the special case where β = 0.5 and show that extinction probability is at a minimum for β > 0.5 by an amount that increases with increasing adult female mortality. Sensitivity analysis showed that the extinction probability was affected most by changes in adult female mortality, followed by the rate of production of pupae. Because females only produce a single offspring approximately every 10 days, imposing a death rate of greater than about 3.5% per day will ensure the eradication of any tsetse population. These mortality levels can be achieved for some species using insecticide-treated targets or cattle-providing thereby a simple, effective and cost-effective method of controlling and eradicating tsetse, and also human and animal trypanosomiasis. Our results are of further interest in the modern situation where increases in temperature are seeing the real possibility that tsetse will go extinct in some areas, without the need for intervention, but have an increased chance of surviving in other areas where they were previously unsustainable due to low temperatures.
Arctic medicine. Tropical medicine, Public aspects of medicine
Hong-Ping Li,1 Wen Su,2 Yang Shu,3 Xiao-Cui Yuan,1 Li-Xue Lin,1 Teng-Fei Hou,1 Hong-Chun Xiang,1 He Zhu,1 Xue-Fei Hu,1 Li Pan,1 Jing-Nan Wu,1 Xian-Fang Meng,1 Hui-Lin Pan,4 Cai-Hua Wu,1,2 Man Li11Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Acupuncture, Wuhan First Hospital, Wuhan, People’s Republic of China; 3Department of Central Laboratory, Affiliated Hospital of Jiangsu University, Zhenjiang 212000, People’s Republic of China; 4Department of Anesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USAPurpose: We determined whether electroacupuncture (EA) reduces Netrin-1-induced myelinated primary afferent nerve fiber sprouting in the spinal cord and pain hypersensitivity associated with postherpetic neuralgia (PHN) through activation of μ-opioid receptors.Methods: PHN was induced by systemic injection of resiniferatoxin (RTX) in rats. Thirty-six days after RTX injection, a μ-opioid receptor antagonist, beta-funaltrexamine (β-FNA) or a κ-opioid receptor antagonist, nor Binaltorphimine (nor-BNI), was injected intrathecally 30 mins before EA, once every other day for 4 times. Mechanical allodynia was tested with von Frey filaments. The protein expression level of Netrin-1 and its receptors (DCC and UNC5H2) were quantified by using western blotting. The myelinated primary afferent nerve fiber sprouting was mapped with the transganglionic tracer cholera toxin B-subunit (CTB).Results: Treatment with 2 Hz EA at “Huantiao” (GB30) and “Yanglingquan” (GB34) decreased the mechanical allodynia at 22 days and the myelinated primary afferent nerve fiber preternatural sprouting into the lamina II of the spinal dorsal horn at 42 days after RTX injection. Also, treatment with 2 Hz EA reduced the protein levels of DCC and Netrin-1 and promoted the expression of UNC5H2 in the spinal dorsal horn 42 days after RTX injection. Furthermore, the μ-opioid receptor antagonist β-FNA, but not the κ-opioid receptor antagonist nor-BNI, reversed the effect of EA on neuropathic pain caused by RTX. In addition, morphine inhibited the Netrin-1 protein level induced by RTX in SH-SY5Y cells.Conclusions: Through activation of μ-opioid receptors, treatment with EA reduces the expression level of DCC and Netrin-1 and changes a growth-permissive environment in spinal dorsal horn into an inhibitory environment by increasing UNC5H2, thus decreasing RTX-caused primary afferent nerve sprouting in the spinal dorsal horn and neuropathic pain.Keywords: postherpetic neuralgia, analgesia, mechanical hyperalgesia, rat, μ-opioid receptors
Eleftheria Polychronidou, Ilias Kalamaras, Andreas Agathangelidis
et al.
Abstract Background Although the etiology of chronic lymphocytic leukemia (CLL), the most common type of adult leukemia, is still unclear, strong evidence implicates antigen involvement in disease ontogeny and evolution. Primary and 3D structure analysis has been utilised in order to discover indications of antigenic pressure. The latter has been mostly based on the 3D models of the clonotypic B cell receptor immunoglobulin (BcR IG) amino acid sequences. Therefore, their accuracy is directly dependent on the quality of the model construction algorithms and the specific methods used to compare the ensuing models. Thus far, reliable and robust methods that can group the IG 3D models based on their structural characteristics are missing. Results Here we propose a novel method for clustering a set of proteins based on their 3D structure focusing on 3D structures of BcR IG from a large series of patients with CLL. The method combines techniques from the areas of bioinformatics, 3D object recognition and machine learning. The clustering procedure is based on the extraction of 3D descriptors, encoding various properties of the local and global geometrical structure of the proteins. The descriptors are extracted from aligned pairs of proteins. A combination of individual 3D descriptors is also used as an additional method. The comparison of the automatically generated clusters to manual annotation by experts shows an increased accuracy when using the 3D descriptors compared to plain bioinformatics-based comparison. The accuracy is increased even more when using the combination of 3D descriptors. Conclusions The experimental results verify that the use of 3D descriptors commonly used for 3D object recognition can be effectively applied to distinguishing structural differences of proteins. The proposed approach can be applied to provide hints for the existence of structural groups in a large set of unannotated BcR IG protein files in both CLL and, by logical extension, other contexts where it is relevant to characterize BcR IG structural similarity. The method does not present any limitations in application and can be extended to other types of proteins.
Computer applications to medicine. Medical informatics, Biology (General)
Objective: to identify characteristics of suicidal behavior and risk factors among men and women with psychiatric disorders. Method: quantitative study of 410 medical records of psychiatric patients receiving treatment, from 1997 to 2014, with descriptive and inferential analysis of the service’s medical records. Undertaken between April – December 2015, in a Psychosocial Care Center in Divinópolis, in the Brazilian state of Minas Gerais. Result:the higher frequency of suicidal behavior among women was, also, the most frequent reason for admission for treatment in the service. Self-poisoning was more common among the women, while hanging was more common among the men. Upon admission for suicidal behavior, the women’s characteristics were mood disorders, and the men’s were disorders due to the use of psychoactive substances. Suicidal behavior in men was associated with family history of suicide, while among women, it was associated with physical or sexual abuse. Conclusion:Evidence was found for specific characteristics of suicidal behavior among psychiatric patients receiving treatment in relation to gender.