Contemporary review on spontaneous coronary artery dissection: insights into the angiographic finding and differential diagnosis.

Spontaneous coronary artery dissection (SCAD), although in the majority of cases presents as an acute coronary syndrome (ACS), has different pathophysiology from atherosclerosis that influences specific angiography findings and enables most patients to be solved by optimal medical therapy rather than percutaneous coronary intervention (PCI). Therefore, accurate diagnosis is essential for adequate treatment of each patient as management of SCAD differs from that of ACS of atherosclerotic aetiology. So far, invasive coronary angiography remains the most important diagnostic tool in suspected SCAD. However, there are ambiguous cases that can mimic SCAD. In this review, the authors summarize current knowledge about the diagnostic algorithms, particularly angiographic features of SCAD, pitfalls of angiography, and the role of intracoronary imaging in the context of SCAD diagnosis. Finally, apart from the pathognomonic angiographic features of SCAD that are thoroughly discussed in this review, the authors focus on obscure angiography findings and findings that can mimic SCAD as well. Differential diagnosis and the timely recognition of SCAD are crucial as there are differences in the acute and long-term management of SCAD and other causes of ACS.

The influence of the morphometric parameters of the intercondylar notch on occurrence of meniscofemoral ligaments.

BACKGROUND: The purpose of this study was to examine the existence of correlation between the morphometric parameters of the intercondylar notch of the femur and the occurrence of meniscofemoral ligaments (MFLs) and if there is any relationship in the running angle (RA) value between narrowed and normal sized intercondylar notch. MATERIALS AND METHODS: Coronal, sagittal and horizontal magnetic resonance (MR) images of 90 patients with specified exclusion criteria were included in this study. The c2 test was used for statistical analysis. In our research either one or both MFLs were identified in 70 (77.8%) of the 90 coronal MR images. In normal sized intercondylar notch, MFLs was seen in 39 (43.3%) cases and on 31 (34.4%) MR images with narrowed intercondylar notch. RESULTS: A significant correlation was established between the occurrence of the MFL and morphometric parameters of the intercondylar notch (p < 0.05). In normal sized intercondylar notch, 12 posterior meniscofemoral ligaments (pMFLs) of type I were detected (RA value 42°), 8 of type II (RA value 33°), 5 of type III (RA value 23°) and two were of indeterminate type, whilst 10 anterior meniscofemoral ligaments (aMFLs) were of type I (RA value 39°), 7 of type II (RA value 31°), 2 of type III (RA value 25°) and the remaining 6 were indeterminate. In narrowed intercondylar notch, 10 ligaments of pMFLs were of type I (RA value 30°), 8 of type II (RA value 25°), 5 of type III (RA value 20°), 10 ligaments of aMFLs were of type I (RA value 35°) and 9 were indeterminate. Statistically significant differences in the value of the running angle of pMFL type I and of type II were evaluated between two groups with different shaped intercondylar notch (p < 0.05). CONCLUSIONS: The results shown in our study may be useful in medical clinical practice, reconstructive surgery, interpretation of knee MR images as well as genetic research.

Evaluation of solid carvedilol-loaded SMEDDS produced by the spray drying method and a study of related substances.

In this study, various formulations of solidified carvedilol-loaded SMEDDS with high SMEDDS loading (up to 67% w/w) were produced with the spray drying process using various porous silica-based carriers. The process yield was improved with higher atomization gas flow rate during the spray drying process and with prolonged mixing time of dispersion of liquid SMEDDS and solid porous carriers prior to the spray drying process. Depending on the choice of the carrier and the SMEDDS:carrier ratio in solid SMEDDS, different drug loading, self-microemulsifying properties, drug release rates, and released drug fractions were obtained. The products exhibited fast drug release due to preserved self-microemulsifying properties and the absence of crystalline carvedilol, which was confirmed with XRD and Raman mapping. A decrease in drug content during the stability study was observed and investigated. This was at least partially attributed to the chemical degradation of the drug. Key degradation products determined by the LC-MS method were amides formed by in situ reaction of carvedilol with fatty acids present in the oily phase of SMEDDS.

Impact of COVID-19 outbreak on hospital admissions and outcome of acute coronary syndromes in a single high-volume centre in southeastern Europe.

BACKGROUND: As coronavirus disease 2019 (COVID-19) has reached pandemic status, authors from the most severely affected countries have reported reduced rates of hospital admissions for patients with acute coronary syndrome (ACS). AIM: The aim of the present study was to investigate the influence of the COVID-19 outbreak on hospital admissions and outcomes in ACS patients in a single high-volume centre in southeastern Europe. METHODS: This retrospective observational study aimed to investigate the number of hospital admissions for ACS, clinical findings at admission, length of hospitalisation, major complications and in-hospital mortality during the COVID-19 outbreak and to compare the data with the same parameters during an equivalent time frame in 2019. For the ST-elevated myocardial infarction (STEMI) subgroup of patients, changes in ischaemic times were analysed as well. RESULTS: There was a significant reduction of 44.3% in the number of patients admitted for ACS during the COVID-19 outbreak when compared with the same period in 2019 (151 vs 271; 95% confidence interval 38.4-50.2, p < 0.01) with a higher mortality rate (13.2% vs 7.2%, p = 0.03). In 2020, patients with non-ST-elevated myocardial infarction presented more often with acute heart failure (3.3% vs 0.7%, p = 0.04). During the COVID-19 outbreak, we observed increases in the total ischaemic time (303 ± 163.4 vs 200.8 ± 156.8 min, p < 0.05) and door-to-balloon time (69.2 ± 58.4 vs 50.5 ± 31.3 min, p < 0.01) in STEMI patients. CONCLUSIONS: These findings should increase the awareness of morbidity and mortality related to missed or delayed treatment of ACS among the public and the healthcare services.

[Dorsal preservation septorhinoplasty]. / Die nasenrückenerhaltende "Dorsal-Preservation"-Septorhinoplastik.

BACKGROUND: Nasal dorsum deprojection is a very important tool in functional and aesthetic rhinoplasty. In classic techniques, resection of dorsal bone and cartilage renders dorsal reconstruction necessary. The concept of dorsal preservation rhinoplasty has been known for more than a century but has experienced a renaissance in recent years, with many critical technical modifications. MATERIALS AND METHODS: We present the latest technique of piezo-assisted dorsal preservation rhinoplasty with subdorsal triangular resection and subdorsal Cottle modification based on clinical experience of 205 cases. Furthermore, the advantages and disadvantages of this technique are discussed and several other current variations are presented. RESULTS AND DISCUSSION: Piezo-assisted osteotomy enables a very precise fracture line and sparing of periosteum, with bone sculpting possible even after mobilization. Subdorsal septal height reduction always precedes completion of the osteotomy and nasal bone mobilization, to ensure patient safety with regard to skull base injury. Using the presented technical modifications, the risk of step deformities in the radix is minimized. In selected patients, dorsal preservation septorhinoplasty enables the surgeon to perform very conservative and precise deprojection of the nose with excellent outcomes, although the spectrum of possible complications is shifted in comparison to classic techniques. CONCLUSION: The preliminary experience of 205 cases with a revision rate of less than 10% is promising. A final evaluation of the technique will only be possible after further studies and evaluation of long-term results.

Concomitant multiple anomalies of renal vessels and collecting system.

Although anomalies of renal vessels and collecting system are relatively frequent, their concomitant occurrence is a rare event. During dissection of a 75-year-old male formalin-embalmed cadaver, we found multiple variations in the renal vessels and renal collecting system. Both kidneys were normal in size and anteriorly malrotated, with duplex collecting system and duplex ureter. One ureter drained the upper part of the kidney and the second ureter drained the lower part of the kidney. Superior and inferior collecting systems were separated by renal parenchyma. The right kidney had two renal arteries, the first renal artery (main renal artery) originating from the abdominal aorta, passing behind the inferior vena cava (IVC) and entering the kidney through the superior and inferior renal hilum. The second artery was the inferior polar artery. In addition, the right kidney had two renal veins as well. Three renal tributaries emerged from the upper and lower portion of the right renal hilum, and they joined to form the main renal vein which drained into the IVC. The lower renal vein was the inferior polar vein. The left kidney had four renal arteries (two hilar arteries and two polar arteries). The main left renal vein emerged from both superior and inferior left renal hilum, passed in front of the abdominal aorta and drained into the IVC. The left kidney also had the inferior polar vein which was divided behind the aorta (retro aortic vein) into two venous trunks. These venous trunks drained separately into posteromedial aspect of the IVC. Finally, the right testicular vein was formed by two tributaries and drained into the IVC, whereas the two left testicular veins drained separately into the left main renal vein.

Identification of the sulfotransferase iso-enzyme primarily responsible for the bio-activation of topical minoxidil.

Pattern hair loss (i.e., androgenetic alopecia) is a common condition afflicting approximately fifty percent of men and women by the age of fifty. Currently, topical minoxidil is the only US FDA approved drug for the treatment of pattern hair loss in men and women.

[Comparison of piezoelectric and conventional osteotomy in rhinoplasty : A systematic review]. / Vergleich von piezoelektrisch assistierter und konventioneller Osteotomie bei der Rhinoplastik : Ein systematisches Review.

BACKGROUND: Postoperative periorbital edema and ecchymosis after rhinoplasty are mainly caused by the osteotomy with hammer and chisel. The introduction of piezoelectric surgery could lead to a better early postoperative outcome due to improved preservation of soft tissues. The aim of this systematic review was to evaluate the methods and results of studies comparing conventional osteotomy to piezoelectric osteotomy. METHODS: A systematic literature search was conducted in the PubMed/MEDLINE and Google Scholar databases. In the primary selection, all studies on the comparison of conventional and piezoelectric osteotomies with regard to postoperative periorbital edema and/or ecchymosis were identified. Secondary selection included only study designs with a control group. RESULTS: Primary selection resulted in 15 thematically relevant publications with a notable increase in annual publications between 2007 and 2017. Six studies with control groups were selected secondarily. Qualitatively and methodologically, the studies were very heterogeneous. The results of five of the six studies indicated a significant advantage of piezo technology compared to conventional osteotomy. Only in one study was no significant difference found in the investigated postoperative outcome. CONCLUSION: Piezoelectric osteotomy resulted in a reduced propensity for postoperative edema and ecchymosis compared to the conventional osteotomy technique with a chisel. At this time, the results should be regarded as a trend. A definite recommendation favoring piezoelectric osteotomy cannot be made until more studies with higher patient numbers become available.

Empirical equation for preliminary assessment of soil texture.

In this paper, for the first time type and texture of northern Serbian soils were examined using DRIFT spectroscopy. It was investigated whether it is possible to use the specular reflection of the quartz band for the purpose of the preliminary quantitative determination of texture properties. Investigation is conducted on the five most common soil types in Vojvodina: Arenosols, Fluvisols, Chernozems, Vertisols and Solonetz. Spectra were obtained using diffuse reflectance (DRIFT) technique in mid-IR. Spectral characteristics for five characteristic soil types in this region were determined. Certain regularities were observed regarding inorganic bands and main relations between these inorganic components and the texture parameters were determined. The empirical equation for the rough preliminary estimation of the soil texture was determined based on the absorbance values on the 2228 and 1211 cm-1.

Low-dose daily aspirin reduces topical minoxidil efficacy in androgenetic alopecia patients.

Topical minoxidil is the only US FDA approved OTC drug for the treatment of androgenetic alopecia (AGA). Minoxidil is a pro-drug converted into its active form, minoxidil sulfate, by the sulfotransferase enzymes in the outer root sheath of hair follicles. Previously, we demonstrated that sulfotransferase activity in hair follicles predicts response to topical minoxidil in the treatment of AGA. In the human liver, sulfotransferase activity is significantly inhibited by salicylic acid. Low-dose OTC aspirin (75-81 mg), a derivative of salicylic acid, is used by millions of people daily for the prevention of coronary heart disease and cancer. It is not known whether oral aspirin inhibits sulfotransferase activity in hair follicles, potentially affecting minoxidil response in AGA patients. In the present study, we determined the follicular sulfotransferase enzymatic activity following 14 days of oral aspirin administration. In our cohort of 24 subjects, 50% were initially predicted to be responders to minoxidil. However, following 14 days of aspirin administration, only 27% of the subjects were predicted to respond to topical minoxidil. To the best of our knowledge, this is the first study to report the effect of low-dose daily aspirin use on the efficacy of topical minoxidil.

The effect of topical minoxidil treatment on follicular sulfotransferase enzymatic activity.

Minoxidil is the only US FDA-approved topical drug for the treatment of female and male pattern hair loss. Previously, it was demonstrated that topical minoxidil is metabolized to its active metabolite, minoxidil sulfate, by sulfotransferase enzymes located in the outer root sheath of hair follicles. The expression of sulfotransferase in the scalp varies greatly between individuals, and this difference in expression explains the varied response to minoxidil treatment. Previously, we have demonstrated the clinical utility of detecting sulfotransferase in plucked hair follicles to predict minoxidil response in pattern hair loss patients. Typically, exogenous exposure to substrates affects the expression of the enzymatic system responsible for their metabolism. For example, Phase I metabolizing enzymes, such as the cytochrome P450 family of enzymes, are known to be up-regulated in the presence of xenobiotic substrates. However, it is not known if Phase II metabolizing enzymes, such as the sulfotransferase family of enzymes, are similarly affected by the presence of substrates. In this study, we recruited 120 subjects and analyzed their sulfotransferase enzymatic activity before and after treatment with topical minoxidil. Adjusting the results for biologic (within subject) variability, we discovered that the sulfotransferase enzymatic system expression is stable over the course of minoxidil treatment. To the best of our knowledge, this is the first study to demonstrate the stability of sulfotransferase, a Phase II metabolizing enzyme, over the course of minoxidil treatment.

Social selection favours offspring prone to the development of androgenetic alopecia.

In recent years, dermatologists have observed an increase in the incidence of male androgenetic alopecia (AGA). In a survey of 41 dermatologists, 88% reported an increase in incidence of AGA in men younger than 30 years. This phenomenon has no apparent explanation. However, due to the strong genetic inheritance component of AGA, a social or environmental factor which favours the inheritance of genes that increase the risk of developing AGA is suspected. To date, the strongest predictor of AGA in men has been the length of the CAG repeat located in the androgen receptor gene (AR gene) on the X chromosome. The same genetic variant in women is associated with ovulation at a later age, higher antral follicle count, and lower risk for premature ovarian failure. This led us to theorize that, due to social pressure to conceive later in life, women carriers of the short CAG repeat in the AR gene would have a selective advantage to conceive later in life and would thus favour male offspring exhibiting AGA.

Mechanism of action of minoxidil in the treatment of androgenetic alopecia is likely mediated by mitochondrial adenosine triphosphate synthase-induced stem cell differentiation.

Topical minoxidil is the only topical drug approved by the US Food and Drug Administration (FDA) for the treatment of androgenetic alopecia. However, the exact mechanism by which minoxidil stimulates anagen phase and promotes hair growth is not fully understood. In the late telegen phase of the hair follicle growth cycle, stem cells located in the bulge region differentiate and re-enter anagen phase, a period of growth lasting 2-6 years. In androgenetic alopecia, the anagen phase is shortened and a progressive miniaturization of hair follicles occurs, eventually leading to hair loss. Several studies have demonstrated that minoxidil increases the amount of intracellular Ca2+, which has been shown to up-regulate the enzyme adenosine triphosphate (ATP) synthase. A recent study demonstrated that ATP synthase, independent of its role in ATP synthesis, promotes stem cell differentiation. As such, we propose that minoxidil induced Ca2+ influx can increase stem cell differentiation and may be a key factor in the mechanism by which minoxidil facilitates hair growth. Based on our theory, we provide a roadmap for the development of a new class of drugs for the treatment of androgenetic alopecia.

Potential risk of developing herpes simplex encephalitis in patients treated with sildenafil following primary exposure to genital herpes.

Herpes simplex encephalitis (HSE) is associated with significant mortality and morbidity. As a consequence of HSE, up to 75% of infected individuals die or experience irreversible neurological damage. While the pathogenesis of the disease is unknown, it is traditionally hypothesized that the viral infection occurs by neuronal transmission directly from peripheral sites. Non-neuronal modes of infection have generally been overlooked as the brain is protected by the blood-brain-barrier (BBB). The BBB poses an effective barrier to pathogens as well as to drugs such as chemotherapies. In the pursuit to deliver chemotherapeutic agents to the brain, several studies demonstrated that phosphodiesterase type 5 (PDE5) inhibitors, such as sildenafil, may increase the permeability of the BBB enabling successful delivery of chemotherapeutic agents to the brain. In this communication, we report a case of HSE infection in a 62-year-old man, which we suspect was facilitated by the use of sildenafil during a primary genital herpes simple virus (HSV) infection. Due to large number of patients treated with PDE5 inhibitors for erectile dysfunction and the high incidence of genital HSV infection in the general population, a larger study should examine the potential risk of developing HSE in patients treated with PDE5 inhibitors.

Crosstalk Between Enzyme Matrix Metalloproteinases 2 and 9 and Regulatory T Cell Immunity in the Global Burden of Atherosclerosis.

Changes in immune and inflammatory responses may play a crucial role in the development and progression of atherosclerosis, as an autoimmune, chronic and progressive inflammatory disease. Immunological activity and vascular inflammation during atherosclerosis can be modulated by autoimmune responses against self-antigens, according to changeable risk factors (cholesterol, oxidized low-density lipoprotein (ox-LDL) in the vascular wall, fatty acids, etc.), and accompanied by accumulation of leucocytes and proinflammatory cytokines, which stimulate the transcription of matrix metalloproteinases (MMPs), whose concentration are increased in foam cell-rich regions. Regulatory T cells (Tregs) represent a unique subpopulation of T cells specialized in the regulation of immune response and in the suppression of proatherogenic T cells. The aim of our study was to examine the interactions between the concentration of enzyme matrix metalloproteinases 2 and 9 (MMP-2 and 9) in urine and the percentage of Tregs in peripheral blood of two groups of patients: with carotid artery stenosis (CAS), undergoing surgery and with mild atherosclerosis (A) from general practice. The method of enzyme immunoassay (ELISA) was used to determine enzyme MMP expression, and Tregs was examined by flow cytometric analysis. Our data have showed a large increase in the enzyme MMP-2 and 9 in the urine of CAS and A patients in comparison with healthy controls and indicated this method as an easy marker for the monitoring of the development of atherosclerosis. Simultaneously, the diminished number of Tregs in the same patients pointed the importance of these regulatory mechanisms in the etiopathogenesis of atherosclerosis and possible Tregs-mediated therapy.

Melanin of the nipple areola complex.

Biological pigments or biochromes are ubiquitous in animals, plants, and simpler organisms such as fungi and bacteria. They serve a wide spectrum of functions from photosynthesis, camouflage, mimicry, photo protection from the environment to attracting mates. The human female nipple areola complex (NAC) is a highly-pigmented area. Currently, the prevailing theory as to the evolution of the pigmented human NAC is based on infant recognition of breast feeding latching zone; however, due to the protruding shape of the nipple and surrounding breast, the authors of this letter believe that the evolutionary advantage of the pigmented NAC has a direct physiological function, namely the initiation of involution at the end of the infant lactation period.