Beam narrowing test: a motor index of post-stroke motor evaluation in an aged rat model of cerebral ischemia.

Each year, 15 million people worldwide suffer from strokes. Consequently, researchers face increasing pressure to develop reliable behavioural tests for assessing functional recovery after a stroke. Our aim was to establish a new motor performance index that can be used to evaluate post-stroke recovery in both young and aged animals. Furthermore, we validate the proposed procedure and recommend the necessary number of animals for experimental stroke studies. Young (n = 20) and aged (n = 27) Sprague-Dawley rats were randomly assigned to receive either sham or stroke surgery. The newly proposed performance index was calculated for the post-stroke acute, subacute and chronic phases. The advantage of using our test over current tests lies in the fact that the newly proposed motor index test evaluates not only the performance of the unaffected side in comparison to the affected one but also assesses overall performance by taking into account speed and coordination. Moreover, it reduces the number of animals needed to achieve a statistical power of 80%. This aspect is particularly crucial when studying aged rodents. Our approach can be used to monitor and assess the effectiveness of stroke therapies in experimental models using aged animals.

Atypical Histopathological Aspects of Common Types of Lung Cancer-Our Experience and Literature Review.

Lung cancer is among the most common oncological diseases regarding incidence and mortality, with most of these having epithelial origins. Pathological reporting of these tumors is conducted according to the 5th edition of the World Health Organisation (WHO) classification of thoracic tumours. This study aims to draw the pathologist's attention to four rare, atypical microscopic aspects that some of the most common types of lung malignancies reveal upon standard evaluation (hematoxylin-eosin stain) that make histopathological diagnosis challenging: acantholytic, pseudoangiosarcomatous, signet ring cell, and clear cell features. Each of these aspects was exemplified by a case diagnosed in the pathology department of the "Marius Nasta" Institute. Furthermore, we analyzed the classification dynamics of different WHO editions and used PubMed to review articles written in English and published in the last eleven years on this subject. Pathologists should be familiar with these unusual aspects to avoid misdiagnoses and to ensure the correct classification of tumors, which is extremely important because these tumor phenotypes have been associated with specific molecular alterations and a worse clinical evolution. There is a need to clarify the histogenesis and associated genetic mutations, given the fact that the rarity of these tumor phenotypes makes their study difficult. Some authors consider these to be overlapping entities; however, we do not encourage this, as they may exhibit different prognoses and various molecular alterations with important therapeutic implications. The signet ring cell feature was associated with ALK rearrangement in lung adenocarcinoma; thus, these patients can benefit from tailored therapy with ALK-tyrosine kinase inhibitors (ALK-TKI). Recent studies associated clear cell morphology with FGFR3-TACC3 fusion, suggesting that patients with this diagnosis may be potentially eligible for FGFR inhibitors. We described, for the first time, the pseudoangiosarcomatous pattern in a case of lung adenocarcinoma; to our knowledge this aspect has only been described until now in the context of squamous cell carcinomas.

From Molecule to Patient Rehabilitation: The Impact of Transcranial Direct Current Stimulation and Magnetic Stimulation on Stroke-A Narrative Review.

Stroke is a major health problem worldwide, with numerous health, social, and economic implications for survivors and their families. One simple answer to this problem would be to ensure the best rehabilitation with full social reintegration. As such, a plethora of rehabilitation programs was developed and used by healthcare professionals. Among them, modern techniques such as transcranial magnetic stimulation and transcranial direct current stimulation are being used and seem to bring improvements to poststroke rehabilitation. This success is attributed to their capacity to enhance cellular neuromodulation. This modulation includes the reduction of the inflammatory response, autophagy suppression, antiapoptotic effects, angiogenesis enhancement, alterations in the blood-brain barrier permeability, attenuation of oxidative stress, influence on neurotransmitter metabolism, neurogenesis, and enhanced structural neuroplasticity. The favorable effects have been demonstrated at the cellular level in animal models and are supported by clinical studies. Thus, these methods proved to reduce infarct volumes and to improve motor performance, deglutition, functional independence, and high-order cerebral functions (i.e., aphasia and heminegligence). However, as with every therapeutic method, these techniques can also have limitations. Their regimen of administration, the phase of the stroke at which they are applied, and the patients' characteristics (i.e., genotype and corticospinal integrity) seem to influence the outcome. Thus, no response or even worsening effects were obtained under certain circumstances both in animal stroke model studies and in clinical trials. Overall, weighing up risks and benefits, the new transcranial electrical and magnetic stimulation techniques can represent effective tools with which to improve the patients' recovery after stroke, with minimal to no adverse effects. Here, we discuss their effects and the molecular and cellular events underlying their effects as well as their clinical implications.

Evolving Mental Health Dynamics among Medical Students amid COVID-19: A Comparative Analysis of Stress, Depression, and Alcohol Use among Medical Students.

Background and Objectives: The ongoing COVID-19 pandemic has posed an array of new challenges for medical students worldwide. Amidst academic rigors, students are confronted with unique stressors, potentially affecting their mental health and substance use. This study aimed to investigate the multifaceted effects of depression, alcohol use, and stress on medical students and discern how these factors have been amplified by the pandemic's circumstances, and to identify predictors of mental distress during the COVID-19 pandemic period. Materials and Methods: Two online anonymous and cross-sectional surveys were conducted at the University of Medicine and Pharmacy "Iuliu Hatieganu" in Romania among medical students in 2018 and in 2022. Data were gathered via online questionnaires distributed through closed student groups on social media platforms, with a total of 1061 participants, to investigate stress, depression, alcohol and drug use, and the impact of the pandemic and online education on mental health, maintaining anonymity and ethical approval. The Medical Student Stress Questionnaire (MSSQ) was employed to measure different aspects of stress, the Beck Depression Inventory (BDI) provided insights into the participants' depressive symptoms, and for the assessment of alcohol consumption habits, the Alcohol Use Disorders Identification Test (AUDIT) was utilized. Results: Our findings showed a significant decrease in mean depression scores (13.81 vs. 11.56, with p < 0.001) from 2018 to 2022. In 2018, students scored significantly higher in the overall stress-related domains. Additionally, being female, facing financial constraints, and being in pre-clinical years emerged as predictors of heightened academic-related stress and depressive symptoms. Students who had experienced the loss of a family member due to COVID-19 exhibited a statistically significant rise in their average BDI score and current anxiety levels. Conclusions: The pandemic, despite introducing new stressors, may have indirectly fostered an increased focus on students' mental health, leading to more refined support mechanisms. Specialized interventions, taking into account gender and financial problems, are needed to address the multifaceted challenges faced by medical students. Our study highlights the ongoing need to nurture both the academic and emotional strength of future medical practitioners.

New Insights into Boron Essentiality in Humans and Animals.

Boron (B) is considered a prebiotic chemical element with a role in both the origin and evolution of life, as well as an essential micronutrient for some bacteria, plants, fungi, and algae. B has beneficial effects on the biological functions of humans and animals, such as reproduction, growth, calcium metabolism, bone formation, energy metabolism, immunity, and brain function. Naturally organic B (NOB) species may become promising novel prebiotic candidates. NOB-containing compounds have been shown to be essential for the symbiosis between organisms from different kingdoms. New insights into the key role of NOB species in the symbiosis between human/animal hosts and their microbiota will influence the use of natural B-based colon-targeting nutraceuticals. The mechanism of action (MoA) of NOB species is related to the B signaling molecule (autoinducer-2-borate (AI-2B)) as well as the fortification of the colonic mucus gel layer with NOB species from B-rich prebiotic diets. Both the microbiota and the colonic mucus gel layer can become NOB targets. This paper reviews the evidence supporting the essentiality of the NOB species in the symbiosis between the microbiota and the human/animal hosts, with the stated aim of highlighting the MoA and targets of these species.

Adding a First Metatarsal Pin to An Ankle Tubular External Fixator Does Not Reduce the Incidence of Early Reduction Loss.

External fixation with a bilateral frame configuration (delta frame, DF) is a routine approach for treating ankle fractures and dislocations with severe soft tissue damage. The purpose of this study was to evaluate to what extent adding a first metatarsal fixation contributes to the stability of the fixation as evidenced by reduced frequency of early loss of reduction. A retrospective study was performed to compare the rate of early reduction loss in patients treated with a bilateral frame external fixation as part of a 2-stage treatment protocol for periarticular ankle fractures, in a level one trauma center between 2006 and 2016. The cohort was divided into 2 groups according to the frame configuration that had been used: DF only and DF with first metatarsal fixation (DF+1MT). A multivariate analysis assessing risk factors for postoperative loss of reduction was conducted. A total of 67 patients were included in the study, of which 30 underwent fixation by DF and 37 by DF+1MT. Early loss of reduction was recorded in 13 (19.4%) patients, 6 (20%) in the DF group and 7 (18.9%) in the DF+1MT group (p = .576). None of the assessed risk factors reached statistical significance. To conclude, the addition of a first metatarsal pin as an enhancement of external fixation with a delta frame configuration did not reduce the incidence of early loss of reduction. There is no evidence to support the claim that adding this pin contributes to the stability of the fixation in a clinically relevant manner.

Duplication of Inferior Vena Cava, Possible Cause of Internal Hernia? Literature Review and Rare Case Presentation.

Duplication of inferior vena cava (DIVC) is a rare congenital malformation of extreme importance for vascular and urology surgeons, interventional radiologists. Oftentimes it goes unnoticed and is diagnosed incidentally at a routine or emergency CT-scan when complications occur due to associated congenital malformations. We present a case of a 70-year-old male patient who was admitted into the emergency room (ER) accusing abdominal pain. He was diagnosed with an intestinal obstruction due to a left paraduodenal hernia (LPDH), associated with a DIVC. The reviewing the literature led to concluding that DIVC is not the cause of LPDH.

Inhibition of Aquaporin-4 Improves the Outcome of Ischaemic Stroke and Modulates Brain Paravascular Drainage Pathways.

Aquaporin-4 (AQP4) is the most abundant water channel in the brain, and its inhibition before inducing focal ischemia, using the AQP4 inhibitor TGN-020, has been showed to reduce oedema in imaging studies. Here, we aimed to evaluate, for the first time, the histopathological effects of a single dose of TGN-020 administered after the occlusion of the medial cerebral artery (MCAO). On a rat model of non-reperfusion ischemia, we have assessed vascular densities, albumin extravasation, gliosis, and apoptosis at 3 and 7 days after MCAO. TGN-020 significantly reduced oedema, glial scar, albumin effusion, and apoptosis, at both 3 and 7 days after MCAO. The area of GFAP-positive gliotic rim decreased, and 3D fractal analysis of astrocytic processes revealed a less complex architecture, possibly indicating water accumulating in the cytoplasm. Evaluation of the blood vessels revealed thicker basement membranes colocalizing with exudated albumin in the treated animals, suggesting that inhibition of AQP4 blocks fluid flow towards the parenchyma in the paravascular drainage pathways of the interstitial fluid. These findings suggest that a single dose of an AQP4 inhibitor can reduce brain oedema, even if administered after the onset of ischemia, and AQP4 agonists/antagonists might be effective modulators of the paravascular drainage flow.

Bioactive ZnO Coatings Deposited by MAPLE-An Appropriate Strategy to Produce Efficient Anti-Biofilm Surfaces.

Deposition of bioactive coatings composed of zinc oxide, cyclodextrin and cefepime (ZnO/CD/Cfp) was performed by the Matrix Assisted Pulsed Laser Evaporation (MAPLE) technique. The obtained nanostructures were characterized by X-ray diffraction, IR microscopy and scanning electron microscopy. The efficient release of cefepime was correlated with an increased anti-biofilm activity of ZnO/CD/Cfp composites. In vitro and in vivo tests have revealed a good biocompatibility of ZnO/CD/Cfp coatings, which recommend them as competitive candidates for the development of antimicrobial surfaces with biomedical applications. The release of the fourth generation cephalosporin Cfp in a biologically active form from the ZnO matrix could help preventing the bacterial adhesion and the subsequent colonization and biofilm development on various surfaces, and thus decreasing the risk of biofilm-related infections.

Fabrication, Characterization, and Evaluation of Bionanocomposites Based on Natural Polymers and Antibiotics for Wound Healing Applications.

The aim of our research activity was to obtain a biocompatible nanostructured composite based on naturally derived biopolymers (chitin and sodium alginate) loaded with commercial antibiotics (either Cefuroxime or Cefepime) with dual functions, namely promoting wound healing and assuring the local delivery of the loaded antibiotic. Compositional, structural, and morphological evaluations were performed by using the thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and fourier transform infrared spectroscopy (FTIR) analytical techniques. In order to quantitatively and qualitatively evaluate the biocompatibility of the obtained composites, we performed the tetrazolium-salt (MTT) and agar diffusion in vitro assays on the L929 cell line. The evaluation of antimicrobial potential was evaluated by the viable cell count assay on strains belonging to two clinically relevant bacterial species (i.e., Escherichia coli and Staphylococcus aureus).

Epidemiological and Clinical Aspects in a Cohort of Colorectal Cancer Patients.

We conducted a retrospective, observational study, based on 91 patients diagnosed with colorectal cancer (CRC), hospitalized and evaluated within the Surgical and the 2nd Internal Medicine Clinic, the Clinical Emergency County Hospital Craiova, between October 2020 and October 2022. We aimed in this study to analyze the epidemiological aspects and clinical characteristics of patients with CRC. In our study group, the patients' ages were between 30-89 years, with mean a of 68.06 (±9.39) years. The incidence of CRC cases in young patients was relatively low. 56.04% of all patients lived in urban areas. In 57.14% of cases, tumors were found on the left colon. The histopathological (HP) examination revealed the net predominance of adenocarcinoma. Depending on the HP grade, the tumor formations were represented predominantly by moderate and poorly differentiated tumors, having G2 and G3 grades. The T3 tumors predominated the total tumors identified. We observed that obstructions have the highest percentages on the left colon, while haemorrhages and perforations have higher percentages on the right side of the colon. The results obtained in our study largely validated the hypothesis proposed at the beginning of the study, according to which, using the clinical, paraclinical, and HP data, we can create a typology of the patient with CRC, from the Craiova Reference Center, to guide us in identifying some measures to decrease the percentage of CRC, as well as to improve the efficiency of the surgical treatment for these cases.

Diagnostic and Therapeutic Particularities of Symptomatic Melanoma Brain Metastases from Case Report to Literature Review.

The recent introduction of immunotherapy and targeted therapy has substantially enriched the therapeutic landscape of metastatic melanoma. However, cerebral metastases remain unrelenting entities with atypical metabolic and genetic profiles compared to extracranial metastases, requiring combined approaches with local ablative treatment to alleviate symptoms, prevent recurrence and restore patients' biological and psychological resources for fighting malignancy. This paper aims to provide the latest scientific evidence about the rationale and timing of treatment, emphasizing the complementary roles of surgery, radiotherapy, and systemic therapy in eradicating brain metastases, with a special focus on the distinct response of intracranial and extracranial disease, which are regarded as separate molecular entities. To illustrate the complexity of designing individualized therapeutic schemes, we report a case of delayed BRAF-mutant diagnosis, an aggressive forearm melanoma, in a presumed psychiatric patient whose symptoms were caused by cerebral melanoma metastases. The decision to administer molecularly targeted therapy was dictated by the urgency of diminishing the tumor burden for symptom control, due to potentially life-threatening complications caused by the flourishing of extracranial disease in locations rarely reported in living patients, further proving the necessity of multidisciplinary management.

Navigating the Maze: Exploring Non-Oncological Complexities in Non-Small-Cell Lung Cancer.

Pulmonary oncological pathologies are an important public health problem and the association with other pulmonary lesions may pose difficulties in diagnosis and staging or require different treatment options. To address this complexity, we conducted a retrospective observational study at the Marius Nasta Institute of Pneumophthisiology, Bucharest, Romania. Our study focused on patients admitted in 2019 with non-small-cell lung carcinoma and associated pulmonary lesions identified through surgical resection specimens. Among the 314 included patients, multiple pulmonary nodules were observed on macroscopic examination, with 12% (N = 37) exhibiting nonmalignant etiologies upon microscopic examination. These findings underscore the challenge of preoperative staging. Patients with coexisting nonmalignant lesions were similar in age, smoking habits, and professional or environmental exposure by comparison with those who presented only malignant lesions. The presentation of coexisting malignant and nonmalignant lesions may pose difficulties in diagnosing and staging pulmonary cancer.

Immunoexpression of Mismatch Repair Proteins in a Cohort of Colorectal Cancer Patients.

One of the molecular routes of colorectal carcinogenesis is the lack of mismatch repair (MMR) proteins, which may have substantial clinical consequences in predicting therapy success. This study aimed to analyze the expression of the MutL homolog 1 (MLH1), MutS homolog 2 (MSH2), and MutS homolog 6 (MSH6) in a cohort of 91 colorectal cancer (CRC) patients, and to evaluate the relationship between patient clinicopathological characteristics and immunoexpression of these biomarkers. In this study, we obtained the highest scores of the MLH1 immunoexpression in non-mucinous tumors, moderately differentiated lesions, and in stage IV. The highest values of the MSH2 and MSH6 scores were observed in mucinous tumors, and poorly differentiated lesions, in stages II-III, and stages III-IV, respectively. To improve the stratification criteria for targeted oncological therapy and to predict patient outcomes, markers used may help evaluate the aggressiveness of lesions.

Zinc-Boron Complex-Based Dietary Supplements for Longevity and Healthy Life.

The nutritional role of zinc (Zn) and boron (B) in the plant-animal-human food chain is highly topical worldwide research. Our data indicated that Zn-B complex (ZBC)-based dietary supplements can be used as stable non-toxic formulations, with high intestinal absorption rate, inducing alpha2-macroglobulin (A2M) expression for longevity and healthy life. ZBC is metabolized by hydrolysis, mainly at the absorption site (intestinal level), and most of it is excreted in the urine. Within seven hours from the administration in mice, almost the entire amount of orally absorbed ZBC is eliminated in a metabolized form. The highest amount of A2M protein in mouse liver was determined by immunoabsorbance assay in the chronic experiment (1000mg/kg of ZBC), followed by the subchronic experiment (at the same dose of ZBC), and by the acute experiment (5000mg/kg of ZBC).

Investigating the Neuroprotective and Neuroregenerative Effect of Trazodone Regarding Behavioral Recovery in a BL6C57 Mice Stroke Model.

Stroke is a major cause of death and disability worldwide. Between 1990 and 2010, its global burden increased notably with reference to the absolute number of incident events, number of deaths, and disability-adjusted life-years lost. Trazodone is a triazolopyridine derivative that was approved for more than 40 years as monotherapy or in combination with other antidepressant drugs for the treatment of major depressive disorder in adult patients. The aim was investigated if trazodone can improve behavioural outcome after stroke in a mice model of middle cerebral artery occlusion (MCAo) due to the potential neuroprotective and neurodegenerative effects by using three behavioural tests: adhesive tape test, beam test and hole board test. Trazodone administration show modest improvements regarding the motor-sensorial function after stroke especially in the acute post-stroke phase in aged and young animals. The antidepressant effect of the drug was observed in the post-stroke period in aged animals and to a lesser extent in young animals. Future research is needed to evaluate the effects of trazodone at the cellular level to be sure that it has no benefit in stroke patients who do not suffer from depression.

Progress Toward Reversed Uterine Diastolic Flow in the Third Trimester - An Inauspicious Sign.

BACKGROUND: Increased uteroplacental resistance is associated with high uterine artery pulsatility and resistance indices and early diastolic notching. Evolution toward reversed diastolic uterine flow in the third trimester was scarcely reported previously. The feature was related to severe complications for both mother and fetus. MATERIAL AND METHODS: Data were collected from 3638 pregnancies undergoing prenatal care in our hospital. In this study, we aimed to identify those pregnancies with development of a reversed diastolic flow at the spectral Doppler interrogation of uterine arteries later than 24 weeks of gestation. A secondary aim was to follow up and actively manage these pregnancies. RESULTS: Previously, reversed uterine diastolic flow was reported during the third trimester in four cases only. In our study three pregnancies only developed reversed uterine arteries diastolic flow, none being associated with preeclampsia. All cases evolved with complications at birth. CONCLUSIONS: Progressive deterioration of uterine arteries flow is possible during pregnancy. Reversed diastolic flow is a rare occurrence in the third trimester of pregnancy. Based on current knowledge, it may be considered an ominous sign and should trigger a close follow-up. Future studies using routine investigation of uterine arteries flow late in pregnancy may prove informative.

Molecular prognostic factors in colorectal cancer: 5-year follow-up.

Colorectal cancer (CRC) is a frequently diagnosed and lethal disease. The risk of developing CRC is determined by environmental and genetic factors. Surgical treatment is the main curative modality for patients with CRC up to stage III. In recent years, a special place has been given to biological agents used as targeted therapy following the genetic analysis of the tumor: Bevacizumab (Avastin), Cetuximab (Erbitux), Ziv-aflibercept (Zaltrap). We present a study based on 46 colorectal tumor resection specimens from patients operated for CRC in the Surgery Departments of the Emergency County Clinical Hospital of Craiova, Romania. Histopathological examination and immunohistochemistry staining of tissue sections were performed to determine the degree of aggressiveness. Using the Kaplan-Meier test, we calculated the correlation coefficient between survival time and immunohistochemical prognostic factors. The patients were followed for 60 months postoperatively.

Retrospective Study of a Patient with Multiple de Novo Skin Tumor Formations.

In Romania, the incidence of malignant melanocytic tumors is continuously increasing. According to the World Health Organization, the incidence of melanocytic and non-melanocytic skin neoplasms has increased considerably and globally, in the last decade. We present the case of a 49-year-old patient who, over the course of 7 years, came in the Plastic Surgery Clinic of the Emergency County Hospital of Craiova for the excision of a number of 25 skin tumor formations, located on the face, cervical region, trunk and upper limbs. Treatment included complete microsurgical excision and supervision. In the end, the patient's treatment compliance decreased significantly.

A Quick and Comprehensive Guide to Differential Diagnosis of Neck and Back Pain: a Narrative Review.

The list of diagnostic options when approaching a patient with axial pain is impressively complex. Many offer limited diagnostic workups, but we could not find a truly comprehensive diagnostic guide to assist in the diagnostic evaluation. In this short paper, we briefly described a long list of medical conditions, each of which can manifest as back or neck pain, and whose prevalence ranges from common to very rare. We then proposed an algorithm for classifying them into subgroups. Further referral to diagnostic tests and specialist consultations, after assignment to one of those subgroups, could save time and unnecessary tests. We believe that this review and the proposed diagnostic algorithm can be valuable for medical education and for use in the primary care setting for the diagnostic evaluation of any type of back or neck pain in all patient groups.