High Efficacy on the Death of Breast Cancer Cells Using SPMHT with Magnetite Cyclodextrins Nanobioconjugates.

In this study, we present the experimental results obtained in vitro on the human breast adenocarcinoma cell line (MCF-7) by applying superparamagnetic hyperthermia (SPMHT) using novel Fe3O4-PAA-(HP-γ-CDs) (PAA is polyacrylic acid and HP-γ-CDs is hydroxypropyl gamma-cyclodextrins) nanobioconjugates previously obtained by us. In the in vitro SPMHT experiments, we used concentrations of 1, 5 and 10 mg/mL of Fe3O4 ferrimagnetic nanoparticles from Fe3O4-PAA-(HP-γ-CDs) nanobioconjugates suspended in culture media containing 1 × 105 MCF-7 human breast adenocarcinoma cells. The harmonic alternating magnetic field used in the in vitro experiments that did not affect cell viability was found to be optimal in the range of 160-378 Gs and at a frequency of 312.2 kHz. The appropriate duration of the therapy was 30 min. After applying SPMHT with these nanobioconjugates under the above conditions, MCF-7 cancer cells died out in a very high percentage, of until 95.11%. Moreover, we studied the field up to which magnetic hyperthermia can be safely applied without cellular toxicity, and found a new upper biological limit H × f ~9.5 × 109 A/m⋅Hz (H is the amplitude and f is the frequency of the alternating magnetic field) to safely apply the magnetic field in vitro in the case of MCF-7 cells; the value was twice as high compared to the currently known value. This is a major advantage for magnetic hyperthermia in vitro and in vivo, because it allows one to achieve a therapy temperature of 43 °C safely in a much shorter time without affecting healthy cells. At the same time, using the new biological limit for a magnetic field, the concentration of magnetic nanoparticles in magnetic hyperthermia can be greatly reduced, obtaining the same hyperthermic effect, while at the same time, reducing cellular toxicity. This new limit of the magnetic field was tested by us in vitro with very good results, without the cell viability decreasing below ~90%.

Fe3O4-PAA-(HP-γ-CDs) Biocompatible Ferrimagnetic Nanoparticles for Increasing the Efficacy in Superparamagnetic Hyperthermia.

In this paper, we present the obtaining of Fe3O4-PAA-(HP-γ-CDs) ferrimagnetic nanobioconjugates (PAA: polyacrylic acid, HP-γ-CDs: hydroxypropyl gamma-cyclodextrins) in a hybrid core-shell biostructure (core: inorganic Fe3O4 nanoparticles, and shell: organic PAA-(HP-γ-CDs)) and their use in superparamagnetic hyperthermia without cellular toxicity and with increased efficacy for future alternative cancer therapy. In order to design the optimal experimental conditions for obtaining nanobioconjugates and then superparamagnetic hyperthermia (SPMHT), we used molecular docking simulation and computational assessment of the maximum specific loss power (SLP) that led to nanoparticles' heating. The nanoparticles and nanobioconjugates obtained were studied and characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transformed-infrared spectroscopy (FT-IR), dynamic light scattering (DLS), and magnetic measurements (MMs). The cell viability of the nanoparticles and nanobioconjugates was assessed by means of the MTT assay using human immortalized keratinocytes (HaCaT) as an in vitro model. Superparamagnetic hyperthermia with nanoparticles and nanobioconjugates was obtained experimentally in a magnetic field of 15.92 kA/m and frequency of 312.2 kHz for the magnetic nanoparticle core with a (average) diameter of 15.8 nm, which resulted in the maximum hyperthermic effect that led to a temperature of ~42.5 °C necessary in the therapy of tumors in a short time so as not to affect healthy tissues. The biological screening of Fe3O4-PAA nanoparticles and PAA-(HP-γ-CDs) nanobioconjugates showed no cytotoxic effect on HaCaT cells for a time interval of 24 h, both under standard (37 °C) and hyperthermia conditions (42.5 °C). Thus, Fe3O4-PA-(HP-γ-CDs) ferrimagnetic nanobioconjugates can be used successfully in superparamagnetic hyperthermia without toxicity and with increased efficiency due to the small layer thickness of the PAA-(HP-γ-CDs) shell, which is suitable in this alternative therapeutic technique.

The Impact of SARS-CoV-2 Pandemic on Patients with Malignant Melanoma at a Romanian Academic Center: A Four-Year Retrospective Analysis.

Considering cancer patients may be at an increased risk of severe COVID-19 disease, their oncologic treatment cannot be delayed without risking their oncologic outcomes. Considering this, a comprehensive evaluation is required for the management of malignant diseases such as melanoma. The current study aimed to assess the impact of the COVID-19 pandemic on the delivery of cancer care services for patients diagnosed with malignant melanoma in Romania; to document the difference in patients' addressability and melanoma staging between the pandemic and pre-pandemic periods; as well as to determine the risk factors responsible for disease progression during the pandemic. We developed a retrospective analysis using a monocentric hospital database to compare the final 24 months of the pre-pandemic era to the first 24 months of the COVID-19 pandemic. All outpatients and inpatients with a diagnosis of malignant melanoma were screened during the study period and included in the analysis if matching the inclusion criteria. A total of 301 patients were included in the study, with 163 cases identified in the 24 months before the COVID-19 pandemic and 138 patients during the first 24 months of the pandemic. It was observed during the first two lockdown periods from March to May 2020, and, respectively, from October to December 2020, that significantly fewer patients with malignant melanoma presented for specialized medical care, while there was a statistically significantly lower proportion of outpatients due to COVID-19 restrictions (18.1% vs. 42.9%). The average Breslow depth was 1.1 mm before the pandemic, compared with 1.8 mm during the pandemic (p-value < 0.001). Third-stage patients were the most prevalent during both study periods, although with a statistically significant difference during the pandemic, with an increase from 90 (55.2%) patients to 94 (68.1%) (p-value < 0.001). The significant risk factors for disease progression were advanced AJCC stage (HR = 3.48), high Breslow index (HR = 3.19), postponed treatment (HR = 2.46), missed appointments (HR = 2.31), anemia at presentation (HR = 1.60), and patient's age (HR = 1.57). After the pandemic limitations are brought to an end, a broad skin-cancer-screening campaign is warranted to detect the missed cases during COVID-19.

Multidisciplinary design: Creating a common perspective in complex cases.

OBJECTIVE: This clinical report describes and illustrates digital treatment planning and interdisciplinary orthodontic, surgical, and prosthetic treatment in a highly complex clinical case. CLINICAL CONSIDERATIONS: Analogue design protocols through wax ups are highly variable, technique sensitive, and operator dependent. Digital smile design and treatment planning tools facilitate simplified processes through the use of natural tooth libraries, based on the specific esthetic and functional needs of the individual patient. The vast information compiled in the virtual patient and the treatment plan consolidated in the initial digital design facilitate true interdisciplinary treatment planning and execution, with all dental specialties involved, from orthodontic to surgical and prosthetic treatment. CONCLUSIONS: Digital protocols and design tools provide clear clinical roadmaps for increased efficiency, precision, and predictability, vastly improving the quality of interdisciplinary patient care. CLINICAL SIGNIFICANCE: While analogue protocols are technique sensitive and largely dependent on the operator, digital smile design, and treatment planning tools offer opportunities for truly patient-centered individualized care and interdisciplinary treatment.

Surgical management of dissecting cellulitis of the scalp using free latissimus dorsi flap and meshed split-thickness skin graft: A case report.

INTRODUCTION: Dissecting cellulitis of the scalp, or Hoffman disease, is described as an extremely rare condition. Clinically, it is represented by recurrent painful nodules, purulent drainage, interconnected sinus tracts and keloid formation, leading to scaring and cicatricial alopecia. Without a precise diagnosis and an adequate treatment, the repercussions consist of severe infectious complications along with psychological negative effects and serious aesthetic alterations. There is no standard treatment. In refractory cases, surgical management is reported. PATIENT CONCERNS: We report a case of a 65-year-old Caucasian male patient, with a 5-year history of Hoffman disease, who presented with multiple abscesses and sinus tracts of the scalp and patches of alopecia. The lesions were non-responsive to medical treatment. DIAGNOSIS: The diagnosis of DCS has been established on the basis of the clinical appearance and has been confirmed histopathologically. INTERVENTIONS: The patient underwent wide excision of the scalp, followed by reconstruction using free latissimus dorsi flap and covered by meshed split-thickness skin graft. OUTCOMES: Eighteen-month follow-up revealed complete remission of symptoms and lesions along with satisfactory cosmetic result. CONCLUSION: The scope of this case report is to raise awareness of the following aspects: Hoffman disease has an extremely low occurrence rate, a difficult differential diagnosis and no standard therapeutical strategy. It also highlights the effectiveness of scalpectomy and free latissimus dorsi flap covered by meshed split-thickness skin graft in treating a very advanced stage of the disease together with providing a natural contouring of the scalp. Ultimately, it discusses the other treatment alternatives.

The Moderating Role of Personal Resources Between Demands and Ill-Being of Romanian Healthcare Professionals in the COVID-19 Pandemic.

Background and Objectives: The illness caused by the new coronavirus (COVID-19) triggered considerable mental consequences for the medical staff. Our aim was to research whether frontline healthcare workers' positive psychological state-PsyCap-impacts the relationship between anxiety/depression and burnout/mental health complaints. Material and Methods: One hundred twenty-six medical professionals working on the frontline at the Intensive Care Unit and Emergency Department in Romania took validated surveys between March and April 2020. All information was collected online after accessing a link that was received in an email message. The inclusion criteria concerned the categories of healthcare professionals who came into direct contact with patients during the COVID-19 global epidemic through the performed medical act, as well as time spent in the medical field of ICU an EM, namely at least 1 year in the department. We excluded from the research other categories of employees and auxiliary staff, as well as healthcare workers with <1-year experience in the medical field. The moderating role of personal resources (PsyCap) between demands (such as anxiety and depression) and ill-being (burnout and mental health complaints) of healthcare professionals were tested via hierarchical multiple regressions. Results: We tested the moderating role of PsyCap on the relation between anxiety and ill-being. The results indicated that high anxiety predicts lower emotional exhaustion and a low level of mental health complaints about Romanian healthcare professionals when PsyCap is high. The moderating role of PsyCap on the relation between depression and ill-being was tested in the second hypothesis. The results indicated that high depression predicts lower inefficacy and a low level of mental health complaints about Romanian healthcare professionals when PsyCap is increased. Conclusions: PsyCap is a crucial variable that may decrease the impact of anxiety and depression on psychological outcomes such as emotional exhaustion, inefficacy, and psychological problems among Romanian medical professionals working on the frontline during the COVID-19 global epidemic. Thus, psychological interventions that help medical staff gain personal resources are appropriate in the context of the COVID-19 pandemic.

Infodemia: Another Enemy for Romanian Frontline Healthcare Workers to Fight during the COVID-19 Outbreak.

Background and Objectives: The population has been overwhelmed with false information related to the Coronavirus disease (COVID-19) crisis, spreading rapidly through social media and other channels. We aimed to investigate if frontline healthcare workers affected by infodemia show different psychological consequences than frontline clinicians who do not declare to be affected by false news related to the COVID-19 pandemic. Materials and Methods: One hundred twenty-six frontline healthcare workers from the Intensive Care Unit (ICU) and Emergency Departments in Romania completed a survey to assess stress, depression, anxiety, and sleep disorders, between March and April 2020. We split the sample of frontline healthcare workers into two groups based on the self-evaluated criteria: if they were or were not affected by infodemia in their activity. Results: Considering limitations such as the cross-sectional design, the lack of causality relationship, and the sample size, the results show that, the frontline medical workers who declared to be affected by false news were significantly more stressed, felt more anxiety, and suffered more from insomnia than healthcare workers who are not affected by false information related to pandemic time. Conclusions: The infodemia has significant psychological consequences such as stress, anxiety, and insomnia on already overwhelmed doctors and nurses in the outbreak of the COVID-19 crisis. These findings suggest that medical misinformation's psychological implications must be considered when different interventions regarding frontline healthcare workers during the COVID-19 pandemic are implemented.

The Mediating Role of Insomnia and Exhaustion in the Relationship between Secondary Traumatic Stress and Mental Health Complaints among Frontline Medical Staff during the COVID-19 Pandemic.

The outbreak of coronavirus disease (COVID-19) brought significant psychological implications for healthcare professionals. We aimed to investigate the serial mediation effect of insomnia and exhaustion in the relationship between secondary traumatic stress (STS) and mental health complaints among the frontline healthcare professionals during the COVID-19 pandemic. In this cross-sectional study, 126 frontline healthcare workers from Romania completed validated surveys between March and April 2020. PROCESS macros were used to test the proposed hypotheses of the three-path mediation model. We computed the models for insomnia as the first mediator (M1) and exhaustion (M2) as our second mediator. STS was significantly related to insomnia. Insomnia was significantly related to exhaustion, and STS was positively related to exhaustion. In the third model, exhaustion was strongly and positively related to mental health complaints. The total indirect effect was positive, and the sequential indirect impact of STS on mental health complaints via both mediators in series (insomnia and exhaustion) was significant. Secondary traumatic stress had a positive direct effect on mental health complaints. In our limited sample, the results show that frontline medical staff during the COVID-19 outbreak have high STS, which are related to mental health complaints through insomnia and exhaustion.

Cannabis Sativa Revisited-Crosstalk between microRNA Expression, Inflammation, Oxidative Stress, and Endocannabinoid Response System in Critically Ill Patients with Sepsis.

Critically ill patients with sepsis require a multidisciplinary approach, as this situation implies multiorgan distress, with most of the bodily biochemical and cellular systems being affected by the condition. Moreover, sepsis is characterized by a multitude of biochemical interactions and by dynamic changes of the immune system. At the moment, there is a gap in our understanding of the cellular, genetic, and molecular mechanisms involved in sepsis. One of the systems intensely studied in recent years is the endocannabinoid signaling pathway, as light was shed over a series of important interactions of cannabinoid receptors with biochemical pathways, specifically for sepsis. Furthermore, a series of important implications on inflammation and the immune system that are induced by the activity of cannabinoid receptors stimulated by the delta-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) have been noticed. One of the most important is their ability to reduce the biosynthesis of pro-inflammatory mediators and the modulation of immune mechanisms. Different studies have reported that cannabinoids can reduce oxidative stress at mitochondrial and cellular levels. The aim of this review paper was to present, in detail, the important mechanisms modulated by the endocannabinoid signaling pathway, as well as of the molecular and cellular links it has with sepsis. At the same time, we wish to present the possible implications of cannabinoids in the most important biological pathways involved in sepsis, such as inflammation, redox activity, immune system, and epigenetic expression.

Assessment of Metabolic and Nutritional Imbalance in Mechanically Ventilated Multiple Trauma Patients: From Molecular to Clinical Outcomes.

The critically ill polytrauma patient is characterized by a series of metabolic changes induced by inflammation, oxidative stress, sepsis, and primary trauma, as well as associated secondary injuries associated. Metabolic and nutritional dysfunction in the critically ill patient is a complex series of imbalances of biochemical and genetic pathways, as well as the interconnection between them. Therefore, the equation changes in comparison to other critical patients or to healthy individuals, in which cases, mathematical equations can be successfully used to predict the energy requirements. Recent studies have shown that indirect calorimetry is one of the most accurate methods for determining the energy requirements in intubated and mechanically ventilated patients. Current research is oriented towards an individualized therapy depending on the energy consumption (kcal/day) of each patient that also takes into account the clinical dynamics. By using indirect calorimetry, one can measure, in real time, both oxygen consumption and carbon dioxide production. Energy requirements (kcal/day) and the respiratory quotient (RQ) can be determined in real time by integrating these dynamic parameters into electronic algorithms. In this manner, nutritional therapy becomes personalized and caters to the patients' individual needs, helping patients receive the energy substrates they need at each clinically specific time of treatment.

MicroRNA Expression is Associated with Sepsis Disorders in Critically Ill Polytrauma Patients.

A critically ill polytrauma patient is one of the most complex cases to be admitted to the intensive care unit, due to both the primary traumatic complications and the secondary post-traumatic interactions. From a molecular, genetic, and epigenetic point of view, numerous biochemical interactions are responsible for the deterioration of the clinical status of a patient, and increased mortality rates. From a molecular viewpoint, microRNAs are one of the most complex macromolecular systems due to the numerous modular reactions and interactions that they are involved in. Regarding the expression and activity of microRNAs in sepsis, their usefulness has reached new levels of significance. MicroRNAs can be used both as an early biomarker for sepsis, and as a therapeutic target because of their ability to block the complex reactions involved in the initiation, maintenance, and augmentation of the clinical status.

Cutaneous Melanoma-A Long Road from Experimental Models to Clinical Outcome: A Review.

Cutaneous melanoma is a complex disorder characterized by an elevated degree of heterogeneity, features that place it among the most aggressive types of cancer. Although significant progress was recorded in both the understanding of melanoma biology and genetics, and in therapeutic approaches, this malignancy still represents a major problem worldwide due to its high incidence and the lack of a curative treatment for advanced stages. This review offers a survey of the most recent information available regarding the melanoma epidemiology, etiology, and genetic profile. Also discussed was the topic of cutaneous melanoma murine models outlining the role of these models in understanding the molecular pathways involved in melanoma initiation, progression, and metastasis.

Analysis of oxidative stress-related markers in critically ill polytrauma patients: An observational prospective single-center study.

Critically ill polytrauma patients have increased production of free radicals (FRs) and consequent alterations in biochemical pathways, as well as disruption of cellular integrity, due to increased lipid peroxidation. The aim of this study was to investigate several biomarkers associated with increased oxidative stress in critically ill polytrauma patients, and to evaluate the effect of antioxidant treatment on the clinical outcome in these patients. A total of 67 polytrauma patients from an intensive care unit met the selection criteria. Antiox group included 35/67 patients who received antioxidant therapy, while 32/67 patients without antioxidant treatment were considered as control group. Antioxidant therapy consisted of simultaneous administration of Vitamin C (sodium ascorbate) and N-acetylcysteine, through continuous intravenous infusion. Clinical and paraclinical evaluation of the patients was performed daily until discharge or death. At admission, laboratory parameters did not differ significantly between two groups. At discharge/upon death, statistically significant differences in favor of Antiox group were observed in the following parameters: thrombocytes, activated partial thromboplastin time, prothrombin time, total bilirubin, total cholesterol, high-density lipoproteins, low-density lipoproteins, erythrocyte sedimentation rate, interleukin 6 (all p = 0.0001), total protein (p = 0.0005), serum albumin (p = 0.0004), lactate dehydrogenase (p = 0.0006), and C-reactive protein (p = 0.0014). Starting from day 5, the APACHE II score was significantly decreased in Antiox versus control group (p < 0.05). Finally, the sepsis incidence and mortality rate were significantly lower in Antiox group (p < 0.05). Decreasing the level of oxidative stress by antioxidant substances significantly correlated with a better prognosis and outcome in our patients. Further studies should elucidate more clearly the mechanism of action of antioxidants in critically ill polytrauma patients.

Adipose Tissue Graft Improves Early but not Late Stages of Nerve Regeneration.

AIM: The aim of the study was to assess the effect of autologous fat graft on nerve regeneration by means of immunohistochemistry. MATERIALS AND METHODS: The rat sciatic nerve was used; complete transection followed by primary neurorrhaphy was performed on both hind legs, on the left side a processed fat graft was applied, surrounding the nerve. Nerve biopsies were collected and immunohistochemical procedures were performed for glial fibrillary acidic protein (GFAP) and for neurofilament-associated protein(NFAP). RESULTS: At 4 weeks, GFAP-positive cells were observed in the connective tissue formed between the two nerve endings on the left side only. At 10 weeks, GFAP-positive structures were present and exhibited a tendency to become linear on both sides, with an increased density on the left. NFAP-positive expression was present in the left treated limb with a disorganized pattern. CONCLUSION: Adipose tissue led to the stimulation of GFAP-positive Schwann cells, which could have a positive impact on nerve regeneration in the clinical setting.

Pathological assessment of tumor biopsy specimen and surgical sentinel lymph node dissection in patients with melanoma.

INTRODUCTION: Actual trends of cutaneous malignant melanoma show a faster increase then other forms of cancer. Early detection and diagnosis, and accurate pathologic interpretation of the biopsy specimen is extremely important for the treatment and prognosis of clinically localized melanoma. The surgical approach to cutaneous melanoma patients with clinically uninvolved regional lymph nodes remains controversial. MATERIALS AND METHODS: A retrospective study of melanoma cases was conducted in the "Casa Austria" Department of Plastic and Reconstructive Surgery, Emergency County Hospital, Timisoara, Romania. We have analyzed the medical records of 21 patients that underwent surgical treatment for different stages of melanoma in the period 2008-2012. For histopathological diagnosis of melanoma and the sentinel lymph node(s) status, tissular fragments were routinely processed. For the difficult cases, additional immunohistochemical investigation was done. RESULTS: A positive family history was noted in two cases. The presence of different sizes and localization of pigmented nevi was found in 38% of the cases. Different types of melanoma like superficial spreading melanoma, nodular melanoma or lentigo malignant melanoma and acral lentiginous melanoma was described. The surgical treatment consisted in all cases in wide excision of the primary tumor and prophylactic dissection of sentinel lymph node after lymphoscintigraphy examination. A positive biopsy of the sentinel lymph node was noted in 4.9% of the cases. CONCLUSIONS: The surgical treatment combining the wide excision of the primary tumor with respect to safe oncological limits with the prophylactic dissection of sentinel lymph node after lymphoscintigraphy examination had the confirmation done by the pathologic interpretation of the biopsy specimen showing that all the patients had a Breslow index more than 1.5 mm.

Human conchal cartilage and temporal fascia: an evidence-based roadmap from rhinoplasty to an in vivo study and beyond.

Conchal cartilage or cartilage/ temporal fascia composite grafting (DC-F) used for rhinoplasty is applied by plastic surgeons for reconstructive purposes. Previous studies on experimental models such as mice or rabbits have elucidated on the late events following grafting, with tissue specimens being harvested two months after implantation. Early microscopic and molecular events following DC-F grafting are completely unknown. We designed a chick embryo chorioallantoic membrane model for human grafts study, regarding the dynamic observation of graft survival and its mutual interrelation with the chick embryo chorioallantoic membrane microenvironment. The DC-F graft preserved its cartilage component in a normal state compared to cartilage graft-only because of protective factors provided by temporal fascia. Its strong adherence to the cartilage, lack of angiogenic factors and high content of collagen IV-derived fragments with anti-angiogenic effects make the temporal fascia a good protective tissue to prevent implanted cartilage degeneration. The cartilage graft produced high inflammation, stromal fibrosis and activated angiogenic cascade through VEGF-mediated pathways followed by cartilage degeneration. Also, high content of podoplanin from conchal cartilage chondrocytes exerted a major role in inflammation accompanying cartilage graft. The presently employed experimental model allowed us to characterize the early histological and molecular events triggered by temporal fascia, cartilage or composite graft DC-F implanted on chick embryo chorioallantoic membrane. Our microscopic and molecular observations may help explain some post-surgical complications generated after using cartilage alone as biomaterial for nasal augmentation, supporting the use of DC-F composite graft, with the aim to reduce unwanted post-surgical events.