Paediatric Anatomical Models in Radiotherapy Applications.

Anatomical models have key applications in radiotherapy, notably to help understand the relationship between radiation dose and risk of developing side effects. This review analyses whether age-specific computational phantoms, developed from healthy subjects and paediatric cancer patient data, are adequate to model a paediatric population. The phantoms used in the study were International Commission on Radiological Protection (ICRP), 4D extended cardiac torso (XCAT) and Radiotherapy Paediatric Atlas (RT-PAL), which were also compared to literature data. Organ volume data for 19 organs was collected for all phantoms and literature. ICRP was treated as the reference for comparison, and percentage difference (P.D) for the other phantoms were calculated relative to ICRP. Overall comparisons were made for each age category (1, 5, 10, 15) and each organ. Statistical analysis was performed using Microsoft Excel (version 16.59). The smallest P.D to ICRP was for Literature (-17.4%), closely followed by XCAT (26.6%). The largest was for RT-PAL (88.1%). The rectum had the largest average P.D (1,049.2%) and the large bowel had the smallest (2.0%). The P.D was 122.6% at age 1 but this decreased to 43.5% by age 15. Linear regression analysis showed a correlation between organ volume and age to be the strongest for ICRP (R2 = 0.943) and weakest for XCAT (R2 = 0.676). The phantoms are similar enough to ICRP for potential use in modelling paediatric populations. ICRP and XCAT could be used to model a healthy population, whereas RT-PAL could be used for a population undergoing/after radiotherapy.

Organic contaminants levels, distribution and risk assessment in Jeddah marine coastal zone sediments.

Herein, various organic contaminants were determined in surface sediments collected from the Jeddah coastal zone, Saudi Arabia, to assess their levels, origin and probable toxic effects on marine organisms. High hydrocarbons concentrations, indicative of an enhanced pollutant burden, were recorded in the Jeddah Lagoon (mean value 4100 mg/kg for total aliphatic hydrocarbons (∑AHC) and 5800 µg/kg for total polycyclic aromatic hydrocarbons (∑PAH)), whereas mean values in Mena Jeddah were 258 mg/kg for ∑AHC and 615 µg/kg for ∑PAH. By using molecular diagnostic ratios/indices and applying Positive Matrix Factorization, petroleum related pollution seems to predominate in Jeddah lagoons, whereas carcinogenic contaminants of pyrolytic origin were dominant in Mena Jedda. Additionally, municipal wastewaters were identified as a major source of pollution in Jeddah lagoons. Comparison of the concentrations of individual PAHs and polychlorinated biphenyls with sediment quality guidelines indicates that, despite their high total values, adverse biological effects are unlikely to occur.

Local and systemic autoimmune manifestations linked to hepatitis A infection.

Hepatitis A virus (HAV) represents a global burdening infectious agent causing in the majority of cases a self-limiting acute icteric syndrome, the outcome is related to the hepatic substrate and the potential pre-existing damage, whereas a plethora of extra-hepatic manifestations has also been reported. Despite the absence of post- HAV chronicity it has been associated with an additional burden on existing chronic liver diseases. Moreover, the induced immune response and the antigenic molecular mimicry are considered as triggering factors of autoimmunity with regional and distal impact. Diseases such as autoimmune hepatitis, Guillain-Barré syndrome, rheumatoid arthritis, Still's syndrome, Henoch-Schönlein purpura, autoimmune hemolytic anemia, antiphospholipid syndrome, systematic lupus erythematosus or cryoglobulinemic vasculitis have been described in patients with HAV infection. Although the exact mechanisms remain unclear, this review aims to accumulate and clarify the pathways related to this linkage.

Pollution status determination using trace metals and organic contaminants of the water column in coastal areas of the Red Sea and the Gulf of Aqaba: A baseline assessment.

Herein, we aim to provide a baseline assessment of the pollution status of the water column in coastal areas of Saudi Arabia (Red Sea and the Gulf of Aqaba), using trace metals (Cd, Co, Cr, Cu, Ni, Pb and Zn), total petroleum hydrocarbons (TPHs) and polycyclic aromatic hydrocarbons (PAHs), in seawater samples obtained from 71 sampling stations in June-July 2021. Concerning trace metals, the maximum concentrations for Co, Cu and Ni were detected in Al-Shuqaiq, whereas the highest Pb and Zn concentrations were found in the Jeddah lagoon waters. Elevated concentrations of TPHs and the highest sum of PAHs were recorded in surface waters of Al Lith, Jeddah lagoon and Jeddah Mena. Overall, the concentrations of all trace metals, TPHs and individual PAHs for which environmental standards have been stipulated for the Kingdom of Saudi Arabia fall well below the threshold values.

Tritium and radiocarbon in the water column of the Red Sea.

Despite being the busiest transient sea in the world due to the Suez Canal, radionuclide distribution studies in seawater and sediment of the Red Sea remain rare. A sampling expedition in the Red Sea was conducted from June 9 to July 6, 2021, visiting a transect of several deep sampling stations located along the central axis of the basin from the Gulf of Aqaba to the southern Red Sea (near Farasan Island, Saudi Arabia). The collected seawater profile samples were analyzed for tritium, radiocarbon and oxygen-18. The observed tritium levels in surface waters of the Red Sea peaked at 0.3-0.4 TU, similar to the values observed in the western Arabian Sea (decay corrected). The values observed at waters below 150 m were around 0.2 TU, however, at depths of 450 and 750 m, tritium minima (<0.2 TU) were observed, which could be associated with a partial return flow of bottom waters from the southern to the northern Red Sea. At two stations at the depth of about 550 m, deep Δ14C minima were observed as well (-4‰ and -10‰), documenting ongoing transport of carbon in the water column, important for sink of anthropogenic carbon.

Leydig cell aging: Molecular mechanisms and treatments.

Late-onset hypogonadism, resulting from deficiency in serum testosterone (T), affects the health and quality of life of millions of aging men. T is synthesized by Leydig cells (LCs) in response to luteinizing hormone (LH). LH binds LC plasma membrane receptors, inducing the formation of a supramolecular complex of cytosolic and mitochondrial proteins, the Steroidogenic InteracTomE (SITE). SITE proteins are involved in targeting cholesterol to CYP11A1 in the mitochondria, the first enzyme of the steroidogenic cascade. Cholesterol translocation is the rate-determining step in T formation. With aging, LC defects occur that include changes in SITE, an increasingly oxidative intracellular environment, and reduced androgen formation and serum T levels. T replacement therapy (TRT) will restore T levels, but reported side effects make it desirable to develop additional strategies for increasing T. One approach is to target LC protein-protein interactions and thus increase T production by the hypofunctional Leydig cells themselves.

The MaD-CLINYC score: An easy tool for the prediction of the outcome of hospitalized COVID-19 patients.

BACKGROUND: Most outcome-predictive models for COVID-19 patients use hospital admission data, offering a spontaneous mortality risk estimation. We aimed to elaborate on a tool that could be applied repeatedly, thus being more suitable for these patients' rapidly changing clinical course. METHODS: In this prospective study, we evaluated 560 samples derived from 156 patients hospitalized for COVID-19 in a single center. Age >61 years, male sex, comorbidities >2, need for intensive care unit admission, lactate dehydrogenase (LDH) >408 U/L, Neutrophil/Lymphocyte Ratio (NLR) >17, C-reactive protein (CRP) >10 mg/dl, and D-dimers >3,200 ng/ml were incorporated in an eight-scale score (MaD-CLINYC) after optimal scaling, ridge regression, and bootstrapping, which was documented to correlate with outcome independently of one or more samples analyzed, day from admission at sampling, and need for delivery. Validation process was performed over 574 samples derived from three centers. RESULTS: The developing and the validation cohort Area under Curve (AUC) was 0.90 (95 % Confidence Interval: 0.82-0.98) and 0.91 (0.88-0.94), respectively (p =0.822). A MaD-CLINYC score ≥4 had 75 % sensitivity and 81 % specificity to predict fatal outcome. CONCLUSIONS: MaD-CLINYC score is a powerful, feasible, easy-to-use, dynamic tool to assess the risk of the outcome, thus assisting clinicians in close monitoring and timely decisions in COVID-19 hospitalized patients. HIPPOKRATIA 2021, 25 (3):119-125.

Real-time PCR detection of Helicobacter pylori clarithromycin resistance in Thrace, Greece.

BACKGROUND: Growing resistance to clarithromycin is a major concern regarding treating Helicobacter pylori (H. pylori) infection. Resistance rates have a great variation even in different geographic areas within the same country and are associated with point mutations of the microbial 23S rRNA (A2142C, A2142G, and A2143G). Given the absence of available data in Thrace, the objective of this study was to estimate the resistance of H. pylori to clarithromycin and identify specific mutations that contribute to clarithromycin resistance. METHODS: In this prospective study, we enrolled consecutive patients referred for dyspeptic complaints who underwent upper gastrointestinal endoscopy over two years. Gastric biopsies from corpus and antrum were initially tested for the presence of urease by a rapid urease test. Urease positive samples were followed by real-time PCR to confirm the presence of H. pylori and to detect point mutations. RESULTS: A total of one hundred and thirty patients were included in the study (72 women and 58 men). Resistance to clarithromycin was detected at 23.2 %. Neither gender nor age was independently correlated with resistance rate in our patient group. The most common mutations were A2142G and A2143G. CONCLUSIONS: A high rate of H. pylori resistance to clarithromycin was observed in our region, implicating that it should be addressed in accordance with the recommendations provided by national and international guidelines. Molecular testing should be considered an integral tool for effective monitoring in case of suspected antibiotic resistance. HIPPOKRATIA 2021, 25 (2):51-55.

Infarcted ligamentum teres hepatis lipoma mimicking acute abdomen in a female patient: a case report and mini-review of the literature.

Lipomas of the ligamentum teres hepatis are extremely uncommon. There have been only a few cases reported in the literature, including lipomas of the falciform ligament of the liver. Here we report a case of torsion and infarction of a lipoma of the ligamentum teres hepatis in a 43-year-old female patient, who presented with acute epigastric pain, nausea and vomiting. Diagnosis was based on computed tomography and magnetic resonance imaging. Patient underwent exploratory laparoscopy followed by laparoscopic excision of the infracted lipoma. Finally, we also provide a mini-review of the literature in order to highlight that although rare, this pathology should be included in the differential diagnosis of acute abdomen.

Smoking habits and gallbladder disease: a systematic review and meta-analysis study.

BACKGROUND: It has been claimed that smoking is linked with an increased risk for gallbladder disease (GBD); however, related issues need further consolidation and clarification. The present systematic review and meta-analysis aimed to further investigate the potent correlation between GBD and smoking. METHODS: We conducted a comprehensive literature review to identify every study published from January 1989 to December 2019, reporting risk estimates regarding GBD and smoking. The random-effect, generic inverse variance method, according to description by DerSimonian and Laird, was used to compute pooled estimates. We used the Newcastle-Ottawa quality assessment scale to appraise the included studies' quality. RESULTS: Thirty published case-control, cross-sectional, and cohort studies including 4,623,435 individuals met the eligibility criteria and were considered for data synthesis. Compared to the non-smokers, ever smokers had 1.25 times higher odds of developing GBD [95 % confidence interval (CI): 1.09-1.44]; however, increased heterogeneity was observed (I2 =96 %, 95 % CI: 62-100 %, p <0.001). Publication bias was non-significant (Eggers' regression p =0.072). The main sources of heterogeneity, as detected by meta-regression analyzing study characteristics, biases and confounders, were non-adjustment for family history (p =0.007) and alcohol (p =0.020), respectively. Subgroup analysis indicated a comparable risk for GBD as far as current, former and ever smokers are concerned (p =0.520). Quantitative analysis suggested a dose-effect for current smoking and GBD (p =0.010). CONCLUSIONS: Non-smokers were demonstrated to be at a lower risk of presenting GBD when compared with ever smokers; all relevant risk estimates necessitate adjustment for family history and alcohol intake. HIPPOKRATIA 2020, 24(4): 147-156.

Translocator protein (18 kDa): an update on its function in steroidogenesis.

Translocator protein (18 kDa) (TSPO) is a ubiquitous mitochondrial protein. Studies of its responses to drug and endogenous ligands have shown TSPO to be involved either directly or indirectly in numerous biological functions, including mitochondrial cholesterol transport and steroid hormone biosynthesis, porphyrin transport and heme synthesis, apoptosis, cell proliferation, and anion transport. Localised to the outer mitochondrial membrane of steroidogenic cells, TSPO has been shown to associate with cytosolic and mitochondrial proteins as part of a large multiprotein complex involved in mitochondrial cholesterol transport, the rate-limiting step in steroidogenesis. There is general agreement as to the structure and pharmacology of TSPO. Stimulation of TSPO has been shown to have therapeutic use as anxiolytics by inducing allopregnanolone production in the brain, and also potentially for re-establishing androgen levels in hypogonadal ageing animals. Until recently, there has been general agreement regarding the role of TSPO in steroidogenesis. However, recent studies involving genetic depletion of TSPO in mice have created controversy about the role of this protein in steroid and heme synthesis. We review the data on the structure and function of TSPO, as well as the recent results obtained using various genetic animal models. Taken together, these studies suggest that TSPO is a unique mitochondrial pharmacological target for diseases that involve increased mitochondrial activity, including steroidogenesis. Although there is no known mammalian species that lacks TSPO, it is likely that, because of the importance of this ancient protein in evolution and mitochondrial function, redundant mechanisms may exist to replace it under circumstances when it is removed.

Prenatal phthalate exposure: epigenetic changes leading to lifelong impact on steroid formation.

Endocrine disruptors (ED) are environmental pollutants that mimic endogenous hormonal signals. Exposure to EDs during fetal and early life is a public health concern because these are periods characterized by high cellular plasticity that influence the physiology and development of disease later in life. Phthalates are plasticizers used in the industry to manufacture polyvinyl chloride products and several consumer products. Di(2-ethylhexyl) phthalate (DEHP) is one of the most produced plasticizers; it is ubiquitously found contaminating the environment, and has been shown to be an ED. Human exposure to phthalates starts during fetal development and continues after birth through contact of the newborn with the environment and contaminated food sources. We used a rat model in which pregnant dams are gavaged with DEHP from gestational day 14 until birth to study the long-term effects of DEHP. This window of fetal exposure results in decreased circulating testosterone and aldosterone levels in adult male offspring and estradiol in the female. The observed steroid changes are likely of an epigenetic origin as DEHP is rapidly cleared after birth. Here, we review the long-term effects of fetal exposure to DEHP with a focus on the molecular and epigenetic changes, including DNA methylation, which may mediate long-term endocrine dysfunction.

Pre-pregnancy maternal obesity in Greece: A case-control analysis.

BACKGROUND-AIMS: Pre-pregnancy obesity may cause significant health implications for both mother and neonate. Our study aims to investigate the association between pre-pregnancy Body Mass Index and the risk for cesarean section, admission to Neonatal Intensive Care Unit, macrosomia and preterm delivery, in a Mediterranean country. STUDY DESIGN: A matched retrospective case control analysis was conducted. SUBJECTS: The study population included all pregnant women (with known Body Mass Index data) who gave birth in the University Hospital of Patras between 1st of January 2003 and 31st of December 2008. OUTCOME MEASURES: Cases were defined as obese (338) or overweight (826) women. RESULTS: Overweight and obese women were at higher risk for cesarean section, NICU admission and preterm delivery (χ(2)(2)=36.877, p<0.001, χ(2) Imes and Burke (2014) =6.586, p=0.037 and χ(2) Imes and Burke (2014) =7.227, p=0.027 respectively). Neonatal mean birthweight was higher among obese and overweight women (p<0.0001). CONCLUSIONS: Both obese and overweight pregnancies should be considered as high risk pregnancies, due to more frequent adverse pregnancy outcomes (cesarean delivery, preterm delivery and NICU admission).

Combined effect of G3139 and TSPO ligands on Ca(2+)-induced permeability transition in rat brain mitochondria.

Permeability of the mitochondrial outer membrane is determined by the activity of voltage-dependent anion channels (VDAC) which are regulated by many factors and proteins. One of the main partner-regulator of VDAC is the 18 kDa translocator protein (TSPO), whose role in the regulation of membrane permeability is not completely understood. We show that TSPO ligands, 1 µM PPIX and PK11195 at concentrations of 50 µM, accelerate opening of permeability transition pores (mPTP) in Ca(2+)-overloaded rat brain mitochondria (RBM). By contrast, PK11195 at 100 nM and anti-TSPO antibodies suppressed pore opening. Participation of VDAC in these processes was demonstrated by blocking VDAC with G3139, an 18-mer phosphorothioate oligonucleotides, which sensitized mitochondria to Ca(2+)-induced mPTP opening. Despite the inhibitory effect of 100 nM PK11195 and anti-TSPO antibodies alone, their combination with G3139 considerably stimulated the mPTP opening. Thus, 100 nM PK11195 and anti-TSPO antibody can modify permeability of the VDAC channel and mPTP. When VDAC channels are closed and TSPO is blocked, permeability of the VDAC for calcium seems to be the highest, which leads to accelerated pore opening.

Microwave endometrial ablation after endometrial curettage for the management of heavy menstrual bleeding.

OBJECTIVES: The aim of the present study was to evaluate the eticacy of microwave endometrial ablation after endometrial curettage, in selected patients with heavy menstrual bleeding. MATERIAL AND METHODS: Thirty-two premenopausal women with heavy menstrual bleeding underwent microwave endometrial ablation at the Department of Obstetrics and Gynecology of the University of Patras Medical School. All patients did not respond to previous medical treatment, had completed their childbearing, and did not desire future fertility. The authors chose endometrial curettage rather than hormonal pretreatment (GnRH analogs, danazol) for endometrial preparation. Posttreatment follow up protocol included physical and ultrasonographic evaluation at three, six, nine, and 12 months for the first year and yearly after. RESULTS: The authors had no cases of uterine perforation, thermal injury to adjacent organs, and infection or sepsis. During follow up, there was a gradual decrease in amenorrhea rate (90.6% - 68.8%) and in satisfaction rate (90.6% - 71.9%). Moreover during follow up, eight women underwent to total abdominal hysterectomy. Among them, seven women had uterine myomas and one woman had adenomyosis. CONCLUSIONS: Endometrial preparation with endometrial curettage seems to be a good alternative to hormonal pretreatment. It has the advantage of avoiding delays, side effects, and cost of hormonal pretreatment. Moreover, microwave endometrial ablation after endometrial curettage is successful and highly acceptable.

The GnRH Antagonist Degarelix Directly Inhibits Benign Prostate Hyperplasia Cell Growth.

Gonadotropin-releasing hormone receptors (GnRHR) have been found in extrapituitary tissues, including the prostate, where they might exert a local effect on tissue growth. Degarelix is a GnRHR antagonist approved for use in patients with prostate cancer (PCa) who need androgen deprivation therapy. The slowing of prostate cell growth is a common goal shared by PCa and benign prostate hyperplasia (BPH) patients, and the effect of degarelix on BPH cells has not yet been investigated. We wanted to evaluate the direct effect of degarelix on human BPH primary cell growth. Gene expression studies performed with BPH (n=11), stage 0 (n=15), and PCa (n=65) human specimens demonstrated the presence of GNRHR1 and GNRHR2 and their respective endogenous peptide ligands. BPH-isolated epithelial and stromal cells were either cultured alone or co-cultured (1:4 or 4:1 ratio of epithelial to stromal cells) and subsequently treated with increasing concentrations of degarelix. Degarelix treatment induced a decrease in cell viability and cell proliferation rates, which occurred in parallel to an increase in apoptosis. Both epithelial and stromal BPH cells are sensitive to degarelix treatment and, interestingly, degarelix is also effective when the cells were growing in a co-culture microenvironment. In contrast to degarelix, the GnRHR agonists, leuprolide and goserelin, exerted no effect on the viability of BPH epithelial or stromal cells. In conclusion, (i) prostate tissues express GNRHR and are a potential target for degarelix; and (ii) degarelix directly inhibits BPH cell growth through a decrease in cell proliferation and an increase in apoptosis. Supporting information for this article is available online at http://www.thieme-connect.de/products.

Leydig cell aging and hypogonadism.

Leydig cell testosterone (T) production is reduced with age, resulting in reduced serum T levels (hypogonadism). A number of cellular changes have been identified in the steroidogenic pathway of aged Leydig cells that are associated with reduced T formation, including reductions in luteinizing hormone (LH)-stimulated cAMP production, the cholesterol transport proteins steroidogenic acute regulatory (STAR) protein and translocator protein (TSPO), and downstream steroidogenic enzymes of the mitochondria and smooth endoplasmic reticulum. Many of the changes in steroid formation that characterize aged Leydig cells can be elicited by the experimental alteration of the redox environment of young cells, suggesting that changes in the intracellular redox balance may cause reduced T production. Hypogonadism is estimated to affect about 5 million American men, including both aged and young. This condition has been linked to mood changes, worsening cognition, fatigue, depression, decreased lean body mass, reduced bone mineral density, increased visceral fat, metabolic syndrome, decreased libido, and sexual dysfunction. Exogenous T administration is now used widely to elevate serum T levels in hypogonadal men and thus to treat symptoms of hypogonadism. However, recent evidence suggests that men who take exogenous T may face increased risk of stroke, heart attack, and prostate tumorigenesis. Moreover, it is well established that administered T can have suppressive effects on LH, resulting in lower Leydig cell T production, reduced intratesticular T concentration, and reduced spermatogenesis. This makes exogenous T administration inappropriate for men who wish to father children. There are promising new approaches to increase serum T by directly stimulating Leydig cell T production rather than by exogenous T therapy, thus potentially avoiding some of its negative consequences.

Identification of hot spots of DNA methylation in the adult male adrenal in response to in utero exposure to the ubiquitous endocrine disruptor plasticizer di-(2-ethylhexyl) phthalate.

Exposure to environmental toxicants during fetal development alters gene expression and promotes disease later in life. Di-(2-ethylhexyl) phthalate (DEHP) is a plasticizer widely used for the manufacturing of consumer products. Exposure to DEHP has been associated with obesity, asthma, and low T levels. In utero exposure of pregnant dams to DEHP from gestational day 14 until birth resulted in reduced levels of serum T and aldosterone in the adult male offspring. Because DEHP is rapidly cleared from the body, the effects observed in the adult are likely epigenetic in origin. Under the same experimental conditions, we used reduced-representation bisulfite sequencing to assess changes in DNA methylation. We identified hot spots of DNA methylation changes primarily within CpG islands followed by shelf regions of the genome known to control regional gene expression. We also identified epigenomic areas responsive to exposure to environmental levels of DEHP and found the chromosomal region that houses genes controlling immune responsiveness to be a primary target of DEHP. These data suggest that DEHP phthalate exposure early in life induces epigenetic changes that may be linked to altered gene expression and function in the adult.

The Validity of the Distress Thermometer in Greek Colon Cancer Patients.

BACKGROUND: Although screening for distress is a crucial part of psycho-social care for cancer patients, there has not been a validation study for this purpose in Greece. The purpose of this study was to evaluate for the first time the psychometric properties of the Greek translation of the Distress Thermometer (DT) and Problem List (PL) in Greek colorectal cancer patients (CRC). METHODS: Participants were 84 CRC inpatients of the 1st Surgical Propedeutic Department of the Aristotle University of Thessaloniki with a mean age of 70.8±9.5 years. Participants completed the DT, PL and the Hospital Anxiety and -Depression Scale (HADS). RESULTS: The Cronbach's alpha coefficient in the DT was 0.795. Patients' mean score in the DT was 5.7±2.74, while the mean number of the reported problems in the PL was 18.85±5.50 and the mean total score of the HADS was 15.61±6.95. ROC-analysis supported that a cut-off score of 7 gives the optimal sensitivity and specificity for the DT. CONCLUSION: The index sample has manifested high levels of distress, which correspond to high need for support and improvement of the patient-provider relationship. This is probably a difficult task, since the Greek healthcare system has minimal experience of providing psycho-oncology care. The present study has indicated that the DT can be reliably used in the Greek clinical setting. Future studies, along with state provision, are essential in order to offer Greek cancer patients state-of-the-art and comprehensive care.