Challenges in Optimizing Nanoplatforms Used for Local and Systemic Delivery in the Oral Cavity.

In this study, we focused on innovative approaches to improve drug administration in oral pathology, especially by transmucosal and transdermal pathways. These improvements refer to the type of microneedles used (proposing needles in the saw), to the use of certain enhancers such as essential oils (which, besides the amplifier action, also have intrinsic actions on oral health), to associations of active substances with synergistic action, as well as the use of copolymeric membranes, cemented directly on the tooth. We also propose a review of the principles of release at the level of the oral mucosa and of the main release systems used in oral pathology. Controlled failure systems applicable in oral pathology include the following: fast dissolving films, mucoadhesive tablets, hydrogels, intraoral mucoadhesive films, composite wafers, and smart drugs. The novelty elements brought by this paper refer to the possibilities of optimizing the localized drug delivery system in osteoarthritis of the temporomandibular joint, neuropathic pain, oral cancer, periodontitis, and pericoronitis, as well as in maintaining oral health. We would like to mention the possibility of incorporating natural products into the controlled failure systems used in oral pathology, paying special attention to essential oils.

Natural Sources of Therapeutic Agents Used in Skin Conditions.

Skin conditions are numerous and often have a major impact on patients' quality of life, and effective and safe treatment is very important. The conventional drugs used for skin diseases are usually corticosteroids and antimicrobial products that can induce various side effects, especially with long-term use, which is why researchers are studying alternatives, especially biologically active natural products. Three products caught our attention: bee venom (BV), due to reported experimental results showing anti-inflammatory, antibacterial, antiviral, antioxidant, antimycotic, and anticancer effects, Ficus carica (FC) due to its demonstrated antioxidant, antibacterial, and anti-inflammatory action, and finally Geranium essential oil (GEO), with proven antifungal, antibacterial, anti-inflammatory, and antioxidant effects. Following a review of the literature, we produced this paper, which presents a review of the potential therapeutic applications of the three products in combating various skin conditions and for skin care, because BV, FC, and GEO have common pharmacological actions (anti-inflammatory, antibacterial, and antioxidant). We also focused on studying the safety of the topical use of BV, FC, and GEO, and new approaches to this. This paper presents the use of these natural therapeutic agents to treat patients with conditions such as vitiligo, melasma, and melanoma, as well as their use in treating dermatological conditions in patients with diabetes.

Calcium, Phosphorus and Magnesium Abnormalities Associated with COVID-19 Infection, and Beyond.

The coronavirus disease (COVID-19) pandemic caused by the novel coronavirus SARS-CoV-2 has had a profound impact on global health, leading to a surge in research to better understand the pathophysiology of the disease. Among the various aspects under investigation, disruptions in mineral homeostasis have emerged as a critical area of interest. This review aims to provide an overview of the current evidence linking calcium, phosphorus and magnesium abnormalities with COVID-19 infection and explores the potential implications beyond the acute phase of the disease. Beyond the acute phase of COVID-19, evidence suggests a potential impact of these mineral abnormalities on long-term health outcomes. Persistent alterations in calcium, phosphorus and magnesium levels have been linked to increased cardiovascular risk, skeletal complications and metabolic disorders, warranting continuous monitoring and management in post-COVID-19 patients.

Surgical Management of Perianal Giant Condyloma Acuminatum of Buschke and Löwenstein: Case Presentation.

INTRODUCTION: The Buschke-Löwenstein tumor (BLT) is an uncommon sexually transmitted ailment attributed to the human papillomavirus (HPV)-usually the 6 or 11 type (90%)-with male predominance and an overall infection rate of 0.1%. BLT or giant condyloma acuminatum is recognized as a tumor with localized aggressiveness, displaying distinctive features: the potential for destructive growth, benign histology, a rate of 56% malignant transformation, and a high rate of recurrence after surgical excision. There are several treatment choices which have been tried, including laser, cryotherapy, radiotherapy, electrocoagulation, immunotherapy, imiquimode, sincatechins, intralesional injection of 5-fluoruracil (5-FU), isolated perfusion, and local or systemic chemotherapy. In the case of an extensive tumor, preoperative chemotherapy or radiotherapy is used for tumor shrinkage, making the debulking procedure safer. HPV vaccines significantly decrease the incidence of genital warts, also decreasing the risk of BLT; HPV-6 and HPV-11 are included in these vaccines. MATERIALS AND METHODS: We present a 53-year-old heterosexual man, hospitalized in our department in June 2021 with a typical cauliflower-like tumor mass involving the perianal region, which progressively increased in size for almost 7 years. The perianal mass was completely removed, ensuring negative surgical margins. The large perianal skin defect which occurred was reconstructed with fascio-cutaneous V-Y advancement flap. There was no need for protective stoma. The literature review extended from January 1980 and December 2022, utilizing Pubmed and Google Scholar as search platforms. RESULTS: Due to the disease's proximity to the anal verge and the limited number of reported cases, arriving at a definitive and satisfactory treatment strategy becomes challenging. The optimal approach entails thorough surgical removal of the lesion, ensuring well-defined surgical margins and performing a wide excision to minimize the likelihood of recurrence. In order to repair the large wound defects, various rotation or advancement flaps can be used, resulting in reduced recovery time and a diminished likelihood of anal stricture or other complications. Our objective is to emphasize the significance of surgical excision in addressing BLT through the presentation of a case involving a substantial perianal condyloma acuminatum, managed successfully with complete surgical removal and the utilization of a V-Y advancement flap technique. In the present case, after 5 months post operation, the patient came back with a buttock abscess, which was incised and drained. After another 5 months, the patient returned for difficult defecation, with an anal stenosis being diagnosed. An anal dilatation and sphincterotomy were carried out, with good postoperative results. CONCLUSIONS: The surgical management of Buschke-Löwenstein tumors needs a multidisciplinary team with specialized expertise. The reconstruction techniques involved can be challenging and may introduce additional complications. We consider aggressive surgery, which incorporates reconstructive procedures, as the standard treatment for Buschke-Löwenstein tumors. This approach aims to achieve optimal surgical outcomes and prevent any recurrence.

Comparative Evaluation of the Clinical Severity of COVID-19 of Vaccinated and Unvaccinated Patients in Southeastern Romania in the First 6 Months of 2022, during the Omicron Wave.

(1) Background: The pandemic wave produced by SARS-CoV-2 Omicron was characterized by milder clinical forms and high contagiousness. The vaccination rate against COVID-19 in Romania was approximately 42%. (2) Objectives: Comparison of the clinical severity in vaccinated patients compared to unvaccinated ones. (3) Methods: A retrospective cohort study was conducted on a group of 699 adult patients confirmed with COVID-19 who presented in the "Sf. Cuvioasa Parascheva" Infectious Diseases Clinical Hospital of Galati, Romania, between 1 January 2022 and 30 June 2022. The study compared the need for hospitalization, reinfections, demographic and comorbidity data, clinical and paraclinical parameters from the initial evaluation, and the ratio of unfavorable developments on subgroups chosen according to the vaccination status. (4) Results and Conclusions: Our study reveals that unvaccinated patients required hospitalization in 54.68% of cases, while fully vaccinated patients had a hospitalization rate of 40.72%, which was significantly lower than that of the unvaccinated group (p = 0.01); patients who received a booster dose had a hospitalization rate of 27.84% (p < 0.01, significantly lower than unvaccinated individuals; p = 0.01, significantly lower than fully vaccinated individuals); and among the four patients who received four doses, none required hospitalization. From the analysis of the two subgroups of hospitalized patients, we observed a significantly higher prevalence of radiological lesions, such as pulmonary opacities in the group of unvaccinated patients and a higher average duration of hospitalization, and serum values of D-dimers and blood-sugar at admission were significantly higher in unvaccinated patients. The higher presence of these parameters, which are indicators of severe progression in clinical studies, in the group of unvaccinated patients suggests the need to include them in the initial evaluation of the unvaccinated patients with COVID-19.The cumulative share of deaths and transfers in the ICU was higher in the group of unvaccinated patients, but the difference between the groups had no statistical significance. This study draws attention to the possibility of severe clinical forms among both vaccinated and unvaccinated populations, especially in the elderly and in patients with multiple comorbidities.

Ulceration and a White Lesion of the Tongue in a Male HIV Positive Patient: A Journey on the Avenue of Differential Diagnoses in Search of a Solution.

Oral lesions are early indicator of immunosuppression, leading to HIV new diagnoses. The type of oral lesions can reveal opportunistic diseases that are correlated with the severity of immune depletion. Highly active antiretroviral therapy decreases the incidence of opportunistic oral infections, whereas a large variety of lesions are frequently experienced in people with HIV. Overlapping pathogenic mechanisms and multiple contributing etiologies are related to unusual, atypical oral lesions that are challenging in the clinical practice. We present a rare case of eosinophilic granuloma of the tongue in an older male HIV patient with severe immunosuppression due to the failure of antiretroviral treatment. Differential diagnoses considered squamous carcinoma, lymphoma, viral, fungal or bacterial infections and autoimmune disorders, as well as the influence of HIV immune disfunctions or the influence of cannabidiol use. The histopathologic and immunohistochemistry examination clarified the inflammatory reactive benign substrate of the lesion, although future survey of the oral lesions is essential.

MRI Findings in Axial Psoriatic Spondylarthritis.

Psoriatic arthritis is a significant medical condition with a high prevalence, a wide variety of non-specific symptoms, and a high degree of overlap with other spondylarthritis disorders, particularly ankylosing spondylitis. Hence, knowledge of the magnetic resonance imaging (MRI) manifestations and a multidisciplinary strategy are required for the better management of these patients. We searched publications from the last 10 years and focused on the most relevant ones which discussed the classification criteria, the MRI characteristics of axial psoriatic arthritis, the importance of MRI for follow up, and the reliability of skin and synovial biopsy. Axial spondylarthritis can be diagnosed and followed up on using the well-established MRI technique and, additionally, a biopsy. The analysis and concordance between them can provide new directions for future studies.

Strategies for Improving Transdermal Administration: New Approaches to Controlled Drug Release.

In this work, we aim to address several strategies to improve transdermal drug delivery, such as iontophoresis, sonophoresis, electroporation and micron. We also propose a review of some transdermal patches and their applications in medicine. TDDs (transdermal patches with delayed active substances) are multilayered pharmaceutical preparations that may contain one or more active substances, of which, systemic absorption is achieved through intact skin. The paper also presents new approaches to the controlled release of drugs: niosomes, microemulsions, transfersomes, ethosomes, but also hybrid approaches nanoemulsions and microns. The novelty of this review lies in the presentation of strategies to improve the transdermal administration of drugs, combined with their applications in medicine, in light of pharmaceutical technological developments.

Sweet Syndrome Associated with Myelodysplastic Syndrome-A Review of a Multidisciplinary Approach.

Sweet syndrome (SS) is a rare disease described as a febrile neutrophilic dermatosis with acute onset, the pathogenesis of which has not yet been elucidated. The syndrome is characterized by the sudden onset of erythematous infiltrated papules or plaques located on the upper body and is associated with fever, leukocytosis and neutrophilia. The lesions show a dense dermal infiltration with mature neutrophils. The condition is responsive to systemic steroids. The central nervous system, bones, muscles, eyes, ears, mouth, heart, lung, liver, kidneys, intestines, and spleen may be affected by SS as extracutaneous manifestations. More and more cases have been found to be associated with malignancies, particularly myelodysplastic syndrome, and, less frequently, other hematologic malignancies or solid tumors. Approximately 21% of patients with SS have an associated malignancy and up to 80% of MASS cases are associated with hematological diseases, predominantly myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Myelodysplastic syndrome is a clonal disease of the bone marrow characterized by inefficient hematopoiesis, dysplasia of the bone marrow and peripheral cytopenias. Affected patients have a high risk of leukemic transformation. After analyzing later studies and current practical aspects regarding MDS-related SS, we suggest an algorithm for evaluating these patients.

Principles of Treatment and Clinical-Evolutionary Peculiarities of Deep Cervical Spaces Suppurations-Clinical Study.

As medical-surgical emergencies, regardless of the causal agent, deep cervical space suppurations are not only a diagnostic challenge, but also a therapeutic one. In some cases, in spite of proper therapeutic measures, extremely severe complications can develop. A 5-year retrospective study (2016-2020) was conducted on a group of 107 patients suffering from cervical suppurations, being hospitalized and treated in the ENT Clinic of the "Sf. Apostol Andrei" Emergency County Hospital of Galați. This research is a clinical-statistical study based on the experience of this ENT clinic and was carried out based on the analysis of the patients' medical records. Descriptive analysis' statistical methods of the data series collected from the clinical observation sheets were used, with the patients' informed consent for the processing of the aforementioned data, with the agreement of the Ethics Commission of the Emergency Clinical Hospital "Sf. Apostol Andrei" Galați and the College of Physicians Galați, România. The patients' clinical and multidisciplinary treatment features included in the study group are presented. The results highlight the clinical particularities of deep cervical space suppurations treatment, including under COVID-19 impact, or with other comorbidities, having consequences on the case mix index increase or directly on the costs, admittance duration and the clinical status of the patient at discharge. The conclusions of the clinical study are based on the fulfillment of the research objectives in terms of treatment and symptomatology of deep cervical space suppurations and under the impact of comorbidities (global health crisis and pandemic, triggering of comorbidities due to health care access difficulty in the context of anti-COVID-19 government-implemented measures and the infection-rate that overburdened the medical system in the early period of the pandemic). Individualized treatment of deep cervical space suppurations is recommended to be approached multidisciplinary. Of particular importance is early diagnosis combined with prompt and correctly instituted multidisciplinary treatment. In this context, an appropriate medical measure that we recommend is patient health education, as it was observed in the clinical study: most times, patients address medical services with advanced disease, hence the generally unfavorable prognosis and outcome (about 25% of patients develop unfavorable prognosis and 4% die).

Post COVID-19 Infection Psychosis: Could SARS-CoV-2 Virus Infection Be a Neuropsychiatric Condition That Triggers Psychotic Disorders? - A Case-Based Short Review.

Corona virus (COVID-19) is an epidemy of respiratory disease caused by a novel corona virus and it was declared by the World Health Organization (WHO) to be a global health pandemic emergency. Due to the neuropsychiatric manifestation of Covid-19 that have been associated with psychotic disorders, in this paper we choose to present a case from "Elena Doamna" Psychiatric Hospital from Galati, Romania and to correlate it with other cases from literature in a mini review presentation. In our paper, we present the case of a patient of 44-year-old men, with no past psychiatric history whose behavior included psycho-motor agitation, perception and thinking disorders, disorganized behaviour, attempted suicide by stabbing. The last perspectives from the two years of pandemic together with psychiatric disease linked the virus infections with psychosis to the main concern that Covid-19 could determine psychiatric disorders. There were also presented same literature studies of patients with no personal pathological history in the psychiatric field which developed psychiatric disorders after COVID-19 infection. SARS-CoV-2 has a psychological impact on the mental health status of the worldwide and, especially when it is associated with psychotic symptoms and can affect the quality-of-life. In some cases, the virus affected the brain and as a result, the psychosis symptoms could be an emerging phenomenon associated with the corona virus. Based on the DSM V and ICD-10 criteria, the diagnosis was of acute psychiatric disorders with symptoms of schizophrenia (F23.1). The case report and review reliefs that there is a causal link between the SARS CoV-2 infection and mental disorders, which is currently being investigated.

Hereditary Hemorrhagic Telangiectasia Associating Neuropsychiatric Manifestations with a Significant Impact on Disease Management-Case Report and Literature Review.

(1) Background: Genetic hereditary hemorrhagic telangiectasia (HHT) is clinically diagnosed. The clinical manifestations and lack of curative therapeutic interventions may lead to mental illnesses, mainly from the depression-anxiety spectrum. (2) Methods: We report the case of a 69-year-old patient diagnosed with HHT and associated psychiatric disorders; a comprehensive literature review was performed based on relevant keywords. (3) Results: Curaçao diagnostic criteria based the HHT diagnosis in our patient case at 63 years old around the surgical interventions for a basal cell carcinoma, after multiple episodes of epistaxis beginning in childhood, but with a long symptom-free period between 20 and 45 years of age. The anxiety-depressive disorder associated with nosocomephobia resulted in a delayed diagnosis and low adherence to medical monitoring. A comprehensive literature review revealed the scarcity of publications analyzing the impact of psychiatric disorders linked to this rare condition, frequently associating behavioral disengagement as a coping strategy, psychological distress, anxiety, depression, and hopelessness. (4) Conclusions: As patients with HHT face traumatic experiences from disease-related causes as well as recurring emergency hospital visits, active monitoring for mental illnesses and psychological support should be considered as part of the initial medical approach and throughout the continuum of care.

COVID-19-related psychiatric manifestations requiring hospitalization: Analysis in older vs. younger patients.

The complex manifestations of COVID-19 include psychiatric symptoms, having multifaceted profiles with varying severity during the acute phase and further during the recovery period. Limited data exist which have analyzed whether there are any age-related differences. A study lot of 89 COVID-19 patients with mild-to-moderate SARS-CoV-2 infection requiring hospitalization for mental issues provided comparative data from two age groups below and above 60 years. The majority of patients had new onset of a mental issue during COVID-19, 24.7% of the total lot being diagnosed with depressive disorder. The senior patient set had a significantly higher prevalence of sleep disorder vs. the younger study group (53.3 vs. 28.8%), depression (33.3 vs. 10.2%) and cognitive impairment (26.7 vs. 8.5%), while patients <60 years of age had a higher prevalence of hallucinations, delirium and bizarre behavior. Psychiatric manifestations are an important part of the symptomatology of COVID-19, sometimes requiring hospitalization. Age-related neuropsychiatric substrate could explain some of these differences between the two study subgroups. Further data are needed to complete the acute and long-term distinctive profiles of COVID-19-related mental illness in older and younger patients.

Oral Mucositis Induced by Chemoradiotherapy in Head and Neck Cancer-A Short Review about the Therapeutic Management and the Benefits of Bee Honey.

Background and Objectives: Oral mucositis, a severe non-hematological complication, can be induced by chemoradiotherapy. It is associated with severe local dysfunction, severely affecting the patient's quality of life; it increases the risk of oral infections and interrupts oncological treatment, thus prolonging the duration and cost of hospitalization. Besides all of the agents used in the prevention and treatment of oral mucositis induced by oncological treatment, can there be found an easier one to administer, with an effective preparation, high addressability, both for adults and paediatric patients, without side effects, and at the same time cheap and easy to purchase? The aim of the present paper is to demonstrate the existence of this product, which is available to everyone, having multiple benefits. Materials and Methods: For the purpose of writing this article, materials were searched in electronic databases in between 2019 and 2021, taking into consideration papers where authors have demonstrated the effectiveness of this product through its topical or systemic use. Results: Numerous studies have highlighted the benefits of honey on oral mucositis. Through its analgesic, anti-inflammatory, anti-cancerous and antibacterial action, honey has proved to have a major impact on the patient's quality of life and nutritional status by promoting tissue epithelialization and healing of the chemoradiotherapy-induced lesions. Conclusions: Superior to many natural agents, bee honey can be successfully used in both preventing and treating oral mucositis. There are currently numerous studies supporting and recommending the use of bee honey in the management of this oncological toxicity.

Paget's disease of bone and megaloblastic anemia in a 72-year-old patient: A case report and systematic literature review.

Paget's disease of bone (PDB) is characterized by abnormal osteoclastic bone resorption with disorganized bone neo-formation, primarily affecting elderly (>55 years) patients. Although the majority of patients are asymptomatic, some patients may experience bone pain due to local periosteal involvement or osteoarthritic lesions in the spine; in addition, limb deformities may lead to secondary gait problems or degenerative joint changes. Anemia has an overall prevalence of 12-17% in elderly adults (>65 years old), with macrocytic anemia being the less common type. Megaloblastic anemia is a macrocytic anemia characterized by the presence of large, immature, nucleated cells (megaloblasts) in the blood, with the most common cause being a deficiency of folate and/or vitamin B12. We herein report the rare case of a 72-year-old male patient exhibiting both these conditions, with the aim of discussing the possible association between the two and, most importantly, the clinical management of the patient in a real-life setting over a period of 10 years. The patient was diagnosed based on clinical symptoms (bone pain), radiological imaging and specific laboratory tests, and received discontinuous courses of bisphosphonates and cyanocobalamin supplementation therapy, based mainly on aggravated symptomatology. A systematic literature review was also performed and revealed not only the scarcity of reports on similar cases, but also the mechanisms that may underlie the possible association of PDB with macrocytic anemia due to vitamin B12 deficiency in elderly patients.

Benefits and adverse events of melatonin use in the elderly (Review).

Melatonin is a hormone secreted by the pineal gland in accordance with the circadian rhythm when the light level decreases. Reduction of melatonin secretion with age may be associated with physiological aging in neurodegenerative diseases by affecting the suprachiasmatic nucleus or of the neuronal pathways of transmission to the pineal gland. A significant decrease in melatonin synthesis has been reported in various disorders and diseases, including cardiovascular diseases, metabolic disorders (particularly diabetes type 2), cancer and endocrine diseases. In addition to the fact, that melatonin is a sleep inducer, it also exerts cytoprotective properties as an antioxidant and free radical scavenger. The therapeutic role of melatonin has been demonstrated in sleep disorders, eye damage and cardiovascular disease. The association between melatonin and ß-blockers has had a positive impact on sleep disorders in clinical trials. Previous studies have reported the anti-inflammatory effect of melatonin by adjusting levels of pro-inflammatory cytokines, including interleukin (IL)-6, IL-1ß and tumor necrosis factor-α. Melatonin treatment has been demonstrated to decrease IL-6 and IL-10 expression levels and efficiently attenuate T-cell proliferation. Currently, there is an inconsistency of scientific data regarding the lowest optimal dose and safety of melatonin for long-term use. The aim of the present review was to summarize the evidence on the role of melatonin in various clinical conditions and highlight the future research in this area.

Dynamics of digital ulcers in systemic sclerosis.

Systemic sclerosis (SSc) is a collagenosis with insufficiently known etiopathogenesis, characterized by microvasculopathy and excessive fibrosis in the context of an autoimmune disorder. The incompletely elucidated pathogenesis and limited therapeutic options, disabling aspects, skin lesions and pain determine important functional and psychological deficiencies which affect the quality of life. It is imperative to observe and correlate individual clinical and paraclinical data to optimize disease management. A group of 22 patients diagnosed with SSc, hospitalized in a university clinic in Bucharest was included in an observational study. The evolution of digital ulcers was evaluated as an indicator of vasculopathy and their status and dynamics were correlated with clinical elements reflecting the fibrotic aspect of the disease. The present study shows that the Raynaud phenomenon is almost always present during the course of the disease, but its presence is not always associated with digital ulcers. The existing data in the literature show that fibrosis is subsequent to vasculopathy, but this study did not reveal causality between these two aspects of pathogenesis. The presence of microstomia and digital contracture was identified in the presence of digital ulcers, but also in their absence. The etiopathogenic mechanisms with multiple unknown involved factors open the opportunity to investigate many aspects of SSc for optimal aiming of therapeutic interventions.

New insights in vitiligo treatments using bioactive compounds from Piper nigrum.

Although vitiligo is one of the most frequently occurring depigmentary disorder, its pathophysiology is still not fully clarified, resulting in the incapacity to find a targeted cure. Most of the treatment options available at the time have an anti-inflammatory or immunosuppressive effect, influencing the immune factor in vitiligo but without having a direct effect on melanocyte differentiation, migration or proliferation. This study shows that Piper nigrum (PN) extract and its main alkaloid, piperine, promote melanocyte proliferation in vivo, being consistent with previous study. A PN fruit extract and pure piperine were integrated in two different ointments and tested on human subjects affected by vitiligo. A number of 9 areas were treated: 3 using the extract, 3 using pure piperine, 1 using travoprost solution, and 2 using an association of travoprost (prostaglandin F2α analogue) solution and our products. Pigmentation was achieved in all the treated areas. The extract caused faster and more remarkable results than the pure piperine. The association of the travoprost solution speed up the process and changed the pigmentation pattern, especially when associated with the PN extract. Our early studies suggest that PN extract may represent, in the future, a new treatment option for vitiligo, especially considering the mild side effects of the tested products and the reduced amount of time needed for repigmentation. However, more studies are needed to validate this experimental data.