Prevalence of Cardiovascular Comorbidities in Patients with Rheumatoid Arthritis.

Background and Objectives: The risk of developing cardiovascular diseases (CVD) in patients suffering from rheumatoid arthritis (RA) is two times higher compared to the general population. The objective of this retrospective study was to determine which cardiovascular complications can appear in men vs. women with rheumatoid arthritis. Early diagnosis and initiation of therapeutic measures to reduce the progression rate of rheumatoid arthritis, while also maintaining an active lifestyle, are the most important problems in young patients. Materials and Methods: We included a number of 200 patients, divided into two groups according to gender (124 women and 76 men) with rheumatoid arthritis, presenting various stages of disease concomitant with cardiovascular complications. We assessed traditional and non-traditional risk factors, as well as electrocardiographic and echocardiographic findings in both groups. Results: All patients presented an atherogenic coefficient over two, indicating a significant risk of atherogenesis. Men had elevated levels of total cholesterol compared with women (≥200 mg/dL; 77.6%-men vs. 25.8%-women, p < 0.001). The participants presented cardiac arrhythmias, especially in the active stage of RA. Women had an increased risk of atrial fibrillation by 2.308 times compared to men (p = 0.020). One of the most important complications found in young women was pulmonary arterial hypertension (p = 0.007). Conclusions: In daily clinical practice, the screening of RA is carried out in sufficiently. This disease is often undiagnosed, and the risk factors remain unassessed. As a result, RA patients continue to present an increased risk of developing CVD.

Multifaceted Role of Matrix Metalloproteinases in Neurodegenerative Diseases: Pathophysiological and Therapeutic Perspectives.

Neurodegeneration is the pathological condition, in which the nervous system or neuron loses its structure, function, or both, leading to progressive degeneration or the death of neurons, and well-defined associations of tissue system, resulting in clinical manifestations. Neuroinflammation has been shown to precede neurodegeneration in several neurodegenerative diseases (NDs). No drug is yet known to delay or treat neurodegeneration. Although the etiology and potential causes of NDs remain widely indefinable, matrix metalloproteinases (MMPs) evidently have a crucial role in the progression of NDs. MMPs, a protein family of zinc (Zn2+)-containing endopeptidases, are pivotal agents that are involved in various biological and pathological processes in the central nervous system (CNS). The current review delineates the several emerging evidence demonstrating the effects of MMPs in the progression of NDs, wherein they regulate several processes, such as (neuro)inflammation, microglial activation, amyloid peptide degradation, blood brain barrier (BBB) disruption, dopaminergic apoptosis, and α-synuclein modulation, leading to neurotoxicity and neuron death. Published papers to date were searched via PubMed, MEDLINE, etc., while using selective keywords highlighted in our manuscript. We also aim to shed a light on pathophysiological effect of MMPs in the CNS and focus our attention on its detrimental and beneficial effects in NDs, with a special focus on Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), multiple sclerosis (MS), and Huntington's disease (HD), and discussed various therapeutic strategies targeting MMPs, which could serve as potential modulators in NDs. Over time, several agents have been developed in order to overcome challenges and open up the possibilities for making selective modulators of MMPs to decipher the multifaceted functions of MMPs in NDs. There is still a greater need to explore them in clinics.

Legal medicine implications in fibrinolytic therapy of acute ischemic stroke.

BACKGROUND: Before the advent of fibrinolytic therapy as a gold standard method of care for cases of acute ischemic stroke in Romania, issues regarding legal medicine aspects involved in this area of medical expertise were already presented and, in the majority of cases, the doctors seem to be unprepared for these situations. MAIN TEXT: The present research illustrates some of the cases in which these aspects were involved, that adressed a clinical center having 6 years of professional experience in the application of fibrinolytic treatment for stroke. The following cases report either situations in which the afore mentioned therapy was not rightfully administrated or legal aspects regarding the obtainment of informed consent. CONCLUSION: Obtaining informed consent is a mandatory procedure, which takes time, to the detriment of application of fibrinolytic treatment.

Orthodontic Pain and Dietary Impact Considering Age Groups: A Comparative Study.

(1) Background: orthodontic treatment can frequently be associated with discomfort and pain, a significant factor contributing to treatment discontinuation. (2) Methods: This study, conducted on 160 orthodontic patients across different age groups, aimed to explore the influence of age on patients' responses to treatment, particularly regarding changes in dietary patterns and weight loss. The patients were categorized into three age groups and assessed through a questionnaire about pain perception, pain latency, dietary changes, and weight loss associated with orthodontic appliances. (3) Results: Younger patients (6-12 years) reported lower pain levels, shorter pain latency and fewer alterations in dietary habits compared to adults (over 18 years). Females over 18 represented a significant portion of the sample, suggesting a self-driven inclination towards orthodontic treatment for aesthetic reasons. Fixed orthodontic appliances induced more significant pain than removable ones. Adults experienced more changes in dietary habits and weight loss than younger individuals. (4) Conclusions: the results provide valuable insights for orthodontic practitioners aiming to mitigate adverse effects and improve overall patient experience during treatment.

Optimizing Atrial Fibrillation Care: Comparative Assessment of Anticoagulant Therapies and Risk Factors.

BACKGROUND AND OBJECTIVES: Atrial fibrillation (AF) is a common arrhythmia associated with various risk factors and significant morbidity and mortality. MATERIALS AND METHODS: This article presents findings from a study involving 345 patients with permanent AF. This study examined demographics, risk factors, associated pathologies, complications, and anticoagulant therapy over the course of a year. RESULTS: The results showed a slight predominance of AF in males (55%), with the highest incidence in individuals aged 75 and older (49%). Common risk factors included arterial hypertension (54%), dyslipidemia, diabetes mellitus type 2 (19.13%), and obesity (15.65%). Comorbidities such as congestive heart failure (35.6%), mitral valve regurgitation (60%), and dilated cardiomyopathy (32%) were prevalent among the patients. Major complications included congestive heart failure (32%), stroke (17%), and myocardial infarction (5%). Thromboembolic and bleeding risk assessment using CHA2DS2-VASc and HAS-BLED scores demonstrated a high thromboembolic risk in all patients. The majority of patients were receiving novel oral anticoagulants (NOACs) before admission (73%), while NOACs were also the most prescribed antithrombotic therapy at discharge (61%). CONCLUSIONS: This study highlights the importance of risk factor management and appropriate anticoagulant therapy in patients with AF, to reduce complications and improve outcomes. The results support the importance of tailored therapeutic schemes, for optimal care of patients with AF.

Epidermoid Cyst of the Uterine Cervix, an Unusual Location: Literature Review and Case Report.

Epidermoid cysts are most often benign cystic lesions, with uterine cervical localisation being very unusual. We present the case of a 52-year-old female patient diagnosed with an epidermoid cyst at the level of the uterine cervix. A bioptic and haemostatic uterine curettage was performed, followed by total hysterectomy with bilateral adnexectomy. The histopathologic analysis and immunohistochemical essay of the resection specimens confirmed the cervical epidermoid cyst. The presence of high-risk HPV (human papillomavirus) was only seen in the cervical mucosa. The exact etiopathogenesis is unknown, but postpartum cell implantation of reminiscent embryonic tissue can be involved in the development of these lesions.

Research on demographic, clinical and paraclinical aspects in pregnant women infected with Toxoplasma gondii.

Toxoplasmosis is a zoonotic disease caused by the Toxoplasma gondii protozoan parasite. The aim of this study was to determine the frequency of acute toxoplasmosis or its presence in the medical history of 240 pregnant women, depending on age and geographical background. The second purpose was to analyze several medical aspects (clinical and paraclinical) in pregnant women with acute toxoplasmosis. The study identified several serological changes including positive toxoplasma IgM, IgG, and IgA antibodies. The chemiluminescence immunoassay (CLIA) method was used to detect T. gondii-specific IgM and IgG antibodies and the enzyme immunoassay (EIA) method to detect T. gondii-specific IgA antibodies. Of the 96 pregnant women (40%) infected with T. gondii, approximately 1/3 had acquired acute infection and 2/3 had a history of prior acute infection (P<0.0001). No statistically significant differences according to age groups (P=0.9384) were found in terms of serological profile. The number of patients with negative serology was significantly higher in urban areas than in rural areas (P<0.0001). The highest incidence among the pregnant women with acute toxoplasmosis with a single chain of ganglia affected was represented by those with the involvement of cervical lymph nodes (75%), the difference compared to the involvement of other chains of ganglia being statistically significant (P=0.0087). All 35 pregnant women with acute toxoplasmosis tested positive for T. gondii-specific IgM antibodies. Most pregnant women with acute T. gondii infection (57.1%) tested negative for T. gondii-specific IgM antibody serum titres within 3-6 months of presentation. The difference compared to other intervals from the moment pregnant women sought care was statistically significant (P=00002). Only 80% of all pregnant women with acute toxoplasmosis tested positive for T. gondii-specific IgA antibodies. Pregnant women with acute toxoplasmosis have a 3.3 times higher risk of pregnancy loss.

Assessing the Role of Lipopolysaccharide (LPS) Receptor (CD14) in Septic Cardiomyopathy: The Value of Immunohistochemical Diagnostics.

Sepsis-induced myocardial dysfunction (SIMD) is one of the major predictors of morbidity and mortality of sepsis. A high percentage of patients with SIMD develop a status similar to cardiogenic shock. A high level of bacterial lipopolysaccharide (LPS) associated with an overexpression of CD14 acts as the trigger for the release of a broad spectrum of cytokines. Our study aimed to understand the correlation between septic cardiomyopathy and CD14 immunohistochemical expression. The study included 29 patients who died of septic shock. Increased values of membranous CD14 and soluble CD14 in the heart tissue were correlated with adverse patient evolution. A high cellular expression of CD14 was noted in the study group vs. the control group (p = 0.0013). Therefore, a close positive association between the amount of LPS related to sCD14 and the cellular expression of mCD14 is probable. By extrapolation, we suggest that a large amount of sCD14 detected in the cardiac tissue will activate the mCD14-TRL4-LBP-LPS complex, which in turn will induce an inadequate immune response, resulting in heart damage proportional to the amount of LPS. CD14 could represent a valuable marker for septic cardiomyopathy; thus, apoptosis of cardiomyocytes could be foreseen by its high value.

Cross-talks among GBA mutations, glucocerebrosidase, and α-synuclein in GBA-associated Parkinson's disease and their targeted therapeutic approaches: a comprehensive review.

Current therapies for Parkinson's disease (PD) are palliative, of which the levodopa/carbidopa therapy remains the primary choice but is unable to modulate the progression of neurodegeneration. Due to the complication of such a multifactorial disorder and significant limitations of the therapy, numerous genetic approaches have been proved effective in finding out genes and mechanisms implicated in this disease. Following the observation of a higher frequency of PD in Gaucher's disease (GD), a lysosomal storage condition, mutations of glycosylceramidase beta (GBA) encoding glucocerebrosidase (GCase) have been shown to be involved and have been explored in the context of PD. GBA mutations are the most common genetic risk factor of PD. Various studies have revealed the relationships between PD and GBA gene mutations, facilitating a better understanding of this disorder. Various hypotheses delineate that the pathological mutations of GBA minimize the enzymatic activity of GCase, which affects the proliferation and clearance of α-synuclein; this affects the lysosomal homeostasis, exacerbating the endoplasmic reticulum stress or encouraging the mitochondrial dysfunction. Identification of the pathological mechanisms underlying the GBA-associated parkinsonism (GBA + PD) advances our understanding of PD. This review based on current literature aims to elucidate various genetic and clinical characteristics correlated with GBA mutations and to identify the numerous pathological processes underlying GBA + PD. We also delineate the therapeutic strategies to interfere with the mutant GCase function for further improvement of the related α-synuclein-GCase crosstalks. Moreover, the various therapeutic approaches such as gene therapy, chaperone proteins, and histone deacetylase inhibitors for the treatment of GBA + PD are discussed.

Rice bran, an off-shoot to newer therapeutics in neurological disorders.

Normal brain functioning involves the interaction of interconnected molecular and cellular activities, which appear to alter normal to abnormal brain functioning when worsened, contributing to the emergence of neurological disorders. There are currently millions of people who are living with brain disorders globally and this will rise if suitable prevention strategies are not explored. Nutraceutical intended to treat numerous health goals with little adverse effect possible together can be more beneficial than pharmaceutical monotherapy for fostering balanced brain functioning. Nutraceutical provides a specific composition of effective macronutrients and micronutrients that are difficult to synthesize in the laboratory. Numerous elements of rice fibers in rice bran are characterized as natural anti-oxidant and having potential anti-inflammatory activity. The rice bran captures interest among the researchers as it is widespread, affordable, and rich in nutrients including protein, fat, carbohydrates, bioactive components, and dietary fiber. This review covers the neuroprotective multiplicity of rice bran and its constituents to deter pathological conditions of the brain and to facilitate balanced brain functioning at the same time.

Physical, Psychological and Sexual Abuse of the Minor in the Families from the Northwestern Region of Romania- Social and Medical Forensics.

BACKGROUND: In Romania, the abuse within the family of the minor child is a widespread phenomenon, its extent is insufficiently known because of ignorance/not reporting all the existing cases. METHODS: The participants of the research are represented by two independent groups from the NW Romania 2007-2011, one for sociological study (1544 parents and 1283 children) and another for forensic statistical study (2761 cases of abused children). The sociological study was carried out by analyzing questionnaires applied in schools located in Bihor County, both to children and parents. The statistical analysis was carried out by studying the cases of the physically, sexually, and psychologically abused minors, recorded at Bihor County Forensic Service. RESULTS: Physical neglect and physical abuse are the most common forms of child abuse. The forensic analysis highlight that most of the victims are male from urban areas. Physical abuse is more common in the 16-18 age group, psychological abuse in children aged between 6-10 yr, and sexual abuse in children under the age of 14 years. Girls were subject to sexual abuse, neglect, and emotional abuse, more frequently in rural areas; boys were most often victims of exploitation, physical, and emotional abuse in both urban and rural areas. CONCLUSION: The results of the study led to the formulation of general guidelines on this phenomenon and highlight the need for proposals to improve the current situation of child abuse within the family.

CD4+ CD25+ regulatory T-cells role in tumor microenvironment of the squamous cell carcinoma.

INTRODUCTION: Squamous cell carcinoma (SCC) is the most common skin cancer with a high rate of death. Different lymphocyte populations play an important role in modulating the immune response in the tumor microenvironment. The increase in the proportion of cluster of differentiation (CD)4+ CD25+ regulatory T-cell (Treg) lymphocytes is associated, in different studies, with the increase of the cell multiplication rate. AIM: To analyze the Treg lymphocyte subpopulations and to correlate the results with the presence of the CD8+ cytotoxic T-cell (Tc) lymphocyte population. MATERIALS AND METHODS: Sixty primary skin SCC specimens were incubated with anti-CD8 (clone SP57) rabbit monoclonal antibody and anti-CD25 (clone 4C9) mouse monoclonal antibody. RESULTS: The ratio of the intratumoral∕peritumoral CD4+ CD25+ forkhead box protein p3 (Foxp3) lymphocytes was 0.46, emphasizing that at tumor margins, where tumor aggressiveness is higher, these lymphocytes subpopulations facilitate tumor progression. The comparative analysis of the tumor microenvironment profile revealed that in the case of intratumoral immune response, the number of Tc-type lymphocytes (CD8+) was 3.34 times higher compared to Treg lymphocytes (p<0001). In the peritumoral area, the number of Tc lymphocytes was 5.05 times higher compared to Treg lymphocytes (p<0001). CONCLUSIONS: Treg lymphocytes inhibition may cause the suppression of the antitumoral cell immune response in the tumor environment. We believe that Treg lymphocytes should represent a focus of interest for a new personalized therapy. New studies are needed to better understand the immune response in the tumor microenvironment.

Current Perspective on the Natural Compounds and Drug Delivery Techniques in Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is one of the debilitating brain tumors, being associated with extremely poor prognosis and short median patient survival. GBM is associated with complex pathogenesis with alterations in various cellular signaling events, that participate in cell proliferation and survival. The impairment in cellular redox pathways leads to tumorigenesis. The current standard pharmacological regimen available for glioblastomas, such as radiotherapy and surgical resection following treatment with chemotherapeutic drug temozolomide, remains fatal, due to drug resistance, metastasis and tumor recurrence. Thus, the demand for an effective therapeutic strategy for GBM remains elusive. Hopefully, novel products from natural compounds are suggested as possible solutions. They protect glial cells by reducing oxidative stress and neuroinflammation, inhibiting proliferation, inducing apoptosis, inhibiting pro-oncogene events and intensifying the potent anti-tumor therapies. Targeting aberrant cellular pathways in the amelioration of GBM could promote the development of new therapeutic options that improve patient quality of life and extend survival. Consequently, our review emphasizes several natural compounds in GBM treatment. We also assessed the potential of drug delivery techniques such as nanoparticles, Gliadel wafers and drug delivery using cellular carriers which could lead to a novel path for the obliteration of GBM.

The morphological characteristics of the physically abused child. Report of a case and literature review.

Child abuse remains a current problem, despite progress in the field of prevention and social assistance. The injuries produced by physical abuse have to be evaluated using scientific methods, in order to be considered as evidences later in Court, but also to ensure the physical and social security of the child. Among the morphological characteristics of the child (on which depends how the lesions are formed, differently in children from adults), there is the strong adherence of the dura mater to the skull bones, this fact preventing the formation of extradural hematomas. Another special aspect is the poor development of skeletal muscle before puberty, which confers poor protection of the internal organs against the traumatic physical agents. This paper presents the particular morphological and histological aspects that can be evidenced by forensic autopsy in children. The study was conducted on a female child, physically assaulted, arrived in the emergency department of the hospital. The death occurred shortly after hospitalization. The investigations revealed multiple external (on the whole body) and internal injuries. According to the statements of those who called the ambulance, the injuries occurred because of falling on the stairs and were considered by the family as being superficial, without requiring medical care. The forensic autopsy, through the external, internal and histopathological examination, highlighted the specific injuries that led to the death, thereby contributing to the elucidation of the tanatogenerative mechanism, of the way the lesions were produced and to the applying the law.

Consequences of analgesics use in early pregnancy: Results of tests on mice.

Self-medication during pregnancy continues to be an issue in developing countries due to poor medical education. The most commonly used drugs are analgesics, mainly acetaminophen (paracetamol, APAP) and, to a lesser extent, ketoprofen (KPF). The aim of the study was to establish whether there are consequences of accidental use of these two drugs during early embryogenesis. The experimental study was performed on 30 pregnant white mice, divided into three groups: a first group to which APAP was administered, a second group to which KPF was administered, and group 3 as a control group. At delivery, the baby mice were examined, and after their first parturition, they were taken into study and examined according to the established protocol. Macroscopic and microscopic examinations of the liver and kidney were performed; liver and renal changes were recorded. Regarding the fertility, the number of fetuses born to mothers that were administered APAP and KPF corresponded to the normal values recorded in this species. Microscopic changes that were found in the kidney were as follows: APAP group - necrosis of the urinary tube, vascular congestions and vascular disorders; KPF group - ectasia, especially in the medullary cavity. Microscopic hepatic changes showed in the APAP group - vascular congestions, vascular disorders and hemosiderin deposits in the Kupffer cells; in the KPF group were found - discrete vascular disorders consisting in sinusoidal capillary ectasia and vascular congestions, as well as the presence of lymphocyte conglomerates. The aforementioned lesions indicate hepatic and renal distress with variable degrees of severity, but they appear to be reversible (the longer the time from the maximum effect of the drug the lower its toxicity).

An important morphological feature of the face: upper lip length.

The oral cavity, including the lips, is considered one of the most important features of the face, taken into consideration when people inter-relate. Upper lip, in particular, can have a great influence on the aspect of a smile, which is why its proportional length and thickness can improve a lot a persons' smile. The aim of this study was to determine the average length of the upper lip in the Caucasian population, considering age and gender. The average upper lip length determined on the lateral skull radiography was 20.25±2.555 mm. The average length of the upper lip was 19.79±1.641 mm in the age category under 12 years and 20.32±2.664 mm in the age category over 12 years. The average length of the upper lip was 19.95±2.4 mm in women and 21.18±2.79 mm in men. We can conclude that women have lower values, while men have higher values of the upper lip length, and that the younger the patient is, the shorter the length of the upper lip is. Moreover, the Caucasian population proved to have a shorter upper lip compared to the Asian or Negroid population.

The importance of the histopathological examination in establishing the diagnosis of delayed splenic rupture. Report of a case and literature review.

In forensic activity, splenic ruptures occur frequently in cases involving abdominal trauma due to road traffic collision, strokes, falls and work accidents. Splenic lesions can occur either immediately after the trauma or within variable timeframes after it, the last scenario being the case of a delayed splenic rupture. Delayed splenic rupture is ranked third in abdominal traumatology frequency, after liver and intestine rupture. Delayed splenic rupture is more frequently the result of abdominal contusions or compressions, rather than the result of direct wounds located in the left flank. In the first stage, an intraparenchymatous hematoma is formed. The second stage occurs within a variable timeframe (between two days and one month), either spontaneously or following a second trauma, when the capsule ruptures leading to secondary peritoneal hemorrhage. In order to correctly determine the chronology of splenic lesions, histopathological (HP) investigations have an important role to play. The presence of hemosiderin highlighted by Hematoxylin-Eosin (HE) staining or special stainings, confirms the diagnosis of delayed splenic rupture. This study will present the case of a 55-year-old male from the countryside, a chronic alcohol consumer, animal care provider, who suffered multiple traumatic injuries four days prior to his death. He was found lying on the ground, presenting an open craniocerebral trauma (CCT) with a bleeding wound on the scalp. The autopsy showed CCT with meningeal hemorrhage and subdural hematoma, along with a splenic rupture presumably produced in two stages. The HP investigations did not reveal the presence of hemosiderin in the tested specimen samples. Using this scientific diagnostic criterion, it was thus confirmed that the splenic rupture occurred after the aggression, in another traumatic stage, the same one where the other thanatogenerator lesions occurred, as a result of the victim's collapse from the same level and hitting the planes with irregular surfaces.

Acral-acroma malignant melanoma. A clinical case report and review of literature.

OBJECTIVE: The main objective of this paper is to emphasize the importance of the early diagnosis of certainty in the cases of acral-acroma malignant melanoma in order to increase the survival rate. METHOD: The paper is a review of specialty literature and presents a clinical case of acral-acroma malignant melanoma. Clinical case: acral-acroma malignant melanoma with confirmed lymph node metastases and possibly secondary remote dissemination to the skin in a male patient aged 16 years. We conducted histo-pathological and immunohistochemical examinations of the collected tissue-fragments. RESULTS: The results obtained from the histochemical and immunohisto-chemical examinations are presented, as well as the problems of differential diagnosis. CONCLUSION: The early diagnosis of certainty significantly increases the survival rate. Knowledge and awareness of the population on the use of preventive measures regarding the occurence of the acral-acroma malignant melanoma is therefore required.

The importance of the histopathological examination in lethal acute intoxication with ethylene glycol. Case report.

Ethylene glycol is a toxic alcohol that is mainly introduced into an organism through the digestive pathway. Its priority toxic metabolites are glycolic acid and oxalic acid. We present the case of a young person, of the male persuasion, without any personal pathological history, found unconscious and presenting signs of violence. The patient is emergency hospitalized presenting coma, convulsive syndrome, severe metabolic acidosis and a positive result for alcoholism. Anamnestic data is extremely poor. The results of the clinical and paraclinical examinations suggest a possible poisoning with toxic alcohols. Despite the drug treatment and the hemodialysis, the evolution is unfavorable, resulting in death one week after admission. Through the forensic examination, the followings were found: cerebral and leptomeningeal edema, focal cerebral microhemorrhages, bronchopneumonia, septic spleen, shock kidney, hepatic fatty dystrophy, excoriated plaques in the head area. The histopathological (HP) examination confirms the macroscopic diagnosis and identifies the presence of calcium oxalate crystals in the kidney tubules. Subsequently, the toxicological examination of the biological samples taken from the corpse at the forensic examination, confirms the presence of the glycolic acid. Postmortem, the investigation conducted by the criminal investigation authorities confirms the oral ingestion of antifreeze. The absence of a positive history, along with alcohol consumption, nonspecific clinical symptomatology and the absence of calcium oxalate in urine are trap elements in the diagnosis of acute ethylene glycol poisoning. The presence of calcium oxalate in tissues, identified through the HP examination, is an extremely important factor when establishing the cause of death.