Significant Decrease In Volume Research Articles

Decline of Sperm Quality over the Last Two Decades in the South of Europe: A Retrospective Study in Infertile Patients.

Semen quality has a direct relation to male fertility. Whether sperm variables in humans have decreased over the last years is still uncertain, with some studies showing a decline and others reporting no changes. In this regard, previous research has suggested that lifestyle and environmental conditions may contribute to this variability, calling for regional studies. The present work is a retrospective, unicentric study that includes semen samples analyzed between 1997 and 2017 at the Parc Taulí Hospital (Barcelona metropolitan area). First, a multivariate analysis including the age as a confounding factor showed a statistically significant decrease in semen volume, pH, progressive motility, morphology and total motile sperm over time. Contrarily, no significant variation in sperm count or concentration was observed. Mean reductions per year were -0.02 mL for volume, -0.57% for progressively motile sperm and -0.72% for sperm with normal morphology. Interestingly, the average annual temperature registered by the Spanish Meteorology Agency negatively correlated to sperm morphology and sperm count (Rs = -0.642; p = 0.002 and Rs = -0.435; p = 0.049, respectively). In conclusion, the present study based on infertile patients from the Barcelona area found a decline in sperm motility and morphology, without effects on sperm count. Changes in temperature appeared to be associated to this decline, but further studies are needed to address the mechanisms linked to the observed variations.

Cancer Cells Upregulate Tau to Gain Resistance to DNA Damaging Agents

Recent reports suggested a role for microtubules in double-strand-DNA break repair. We herein investigated the role of the microtubule-associated protein Tau in radio- and chemotherapy. Noticeably, a lowered expression of Tau in breast cancer cell lines resulted in a significant decrease in mouse-xenograft breast tumor volume after doxorubicin or X-ray treatments. Furthermore, the knockdown of Tau impaired the classical nonhomologous end-joining pathway and led to an improved cellular response to both bleomycin and X-rays. Investigating the mechanism of Tau's protective effect, we found that one of the main mediators of response to double-stranded breaks in DNA, the tumor suppressor p53-binding protein 1 (53BP1), is sequestered in the cytoplasm as a consequence of Tau downregulation. We demonstrated that Tau allows 53BP1 to translocate to the nucleus in response to DNA damage by chaperoning microtubule protein trafficking. Moreover, Tau knockdown chemo-sensitized cancer cells to drugs forming DNA adducts, such as cisplatin and oxaliplatin, and further suggested a general role of Tau in regulating the nuclear trafficking of DNA repair proteins. Altogether, these results suggest that Tau expression in cancer cells may be of interest as a molecular marker for response to DNA-damaging anti-cancer agents. Clinically targeting Tau could sensitize tumors to DNA-damaging treatments.

Evaluation of Antiulcer activity of Alcoholic stem extract of Epipremnum aureum (Linden andre) G.S. Bunting

Plants kingdom provides rich source of bioactive phytochemicals which are effective resources that are screened for deve. This plant is native to South eastern Asia and New Guinea. The plant is popular as traditional anticancer preparation in Malaysia and Singapore. In addition, this plant also finds its application in the treatment of ascites, cancer and skin diseases. The current study was carried out to investigate the anti-ulcer activity of the ethanolic stem extract of Epipremnum aureum in Wister rats. Investigation of antiulcer activity of the ethanolic stem extract of Epipremnum aureum was carried out on pylorus ligated and ethanol induced gastric ulcer models by oral administration of extract at the dose of 100, 200 and 400mg/kg body weight. Parameters such as percentage of inhibition of ulcer, ulcer indices were evaluated in ethanol induced ulcer model using Sucralfate (100mg/kg) as the standard drug, while volume of gastric secretion, free acidity, total acidity, pH were assessed in pylorus ligated ulcer model using Omeprazole (30mg/kg) as standard. The extract showed significant (p<0.05) dose dependant reduction in ulcer indices in ethanol induced ulcer model at the tested doses of 100, 200 and 400mg/kg, exhibiting maximum gastroprotection of 73.94% at the dose of 400mg/kg which were comparable with that of sucralfate which showed gastroprotection of 87.9%. In pylorus ligation induced ulcer model, in comparison with the vehicle control group there was significant decrease in total acidity, free acidity, ulcer index, gastric volume and rise in gastric pH were observed in the animals treated with extract at the doses of 200mg/kg and 400mg/kg. The plant extract showed highest gastroprotectivity of 71.3% at the dose of 400mg/kg whereas standard drug Omeprazole showed 81.5%. This study showed that ethanolic stem extract of Epipremnum aureum exhibits gastroprotective and antiulcer activity. Therefore, not only confirmed the traditional usage in the treatment of gastric ulcers, also provided the proof that this plant extract can be incorporated in the development of phytoformulations for the treatment of ulcers of the stomach.

Chebulic Acid Prevents Hypoxia Insult via Nrf2/ARE Pathway in Ischemic Stroke.

Excessive reactive oxygen species (ROS) production contributes to brain ischemia/reperfusion (I/R) injury through many mechanisms including inflammation, apoptosis, and cellular necrosis. Chebulic acid (CA) isolated from Terminalia chebula has been found to have various biological effects, such as antioxidants. In this study, we investigated the mechanism of the anti-hypoxic neuroprotective effect of CA in vitro and in vivo. The results showed that CA could protect against oxygen-glucose deprivation/reoxygenation (OGD/R) induced neurotoxicity in SH-SY5Y cells, as evidenced by the enhancement of cell viability and improvement of total superoxide dismutase (T-SOD) in SH-SY5Y cells. CA also attenuated OGD/R-induced elevations of malondialdehyde (MDA) and ROS in SH-SY5Y cells. Nuclear factor-E2-related factor 2 (Nrf2) is one of the key regulators of endogenous antioxidant defense. CA acted as antioxidants indirectly by upregulating antioxidant-responsive-element (ARE) and Nrf2 nuclear translocation to relieve OGD/R-induced oxidative damage. Furthermore, the results showed that CA treatment resulted in a significant decrease in ischemic infarct volume and improved performance in the motor ability of mice 24 h after stroke. This study provides a new niche targeting drug to oppose ischemic stroke and reveals the promising potential of CA for the control of ischemic stroke in humans.

Thyroid volume changes following adjuvant radiation therapy for breast cancer

Background and purposeIncidental thyroid gland irradiation frequently occurs in breast cancer patients who receive regional nodal irradiation (RNI) to the supraclavicular (SCV) region. Recent studies suggest hypothyroidism (HT) is a complication of radiation therapy (RT) that includes SCV fields. We retrospectively analyzed patients who received RNI to evaluate thyroid gland evolution following RT as well as its association with the development of HT. Materials and methods61 breast cancer patients received SCV-directed RT between 2007 and 2019 and met inclusion criteria. Thyroid glands were retrospectively contoured on CT simulation and follow-up images. Individual dose-volume histograms were analyzed to determine thyroid volume within and outside specific isodose lines. Relative thyroid volume changes based on different radiation doses were estimated by fusing post-RT scans with CT simulation. Logistic regression was performed to assess thyroid volume changes as a factor in the development of HT. ResultsMedian pre-treatment thyroid volume was 11.8 cc (range: 6.3–74.1 cc) with a median of 42.2 % within the 20 Gy and 23.2 % within the 40 Gy isodose lines. A significant decrease in thyroid volume was noted by 1-year post-treatment (p < 0.0001) and thereafter. By 4 years post-treatment, average thyroid volume was decreased by 29.7 % (range: 2.3–64.4 %). Thyroid volume receiving 40 Gy or higher demonstrated a greater decrease compared to those receiving lower irradiation dosage. HT occurred in 17 patients (27.9 %). Patients who developed HT displayed a larger decrease in the thyroid volume receiving between 20 and 40 Gy at 12 months (p = 0.033). ConclusionOur study demonstrates for the first time that a reduction in thyroid volume may be seen as early as 6 months after SCV-directed RT for breast cancer, which correlates with development of clinical and subclinical HT. Furthermore, a dose-dependent correlation exists between thyroid subvolume reduction and SCV-directed RT in breast cancer patients. As feasible, efforts should be made to reduce the dose to the thyroid in patients who undergo RNI for breast cancer.

A Maternal High-Fat Diet Causes Anxiety-Related Behaviors by Altering Neuropeptide Y1 Receptor and Hippocampal Volumes in Rat Offspring: the Potential Effect of N-Acetylcysteine

The children of obese mothers are known to have a high risk of obesity and metabolic disease and are prone to developing cognitive deficits, although the underlying mechanism is not yet fully understood. This study investigated the relationship between neuropeptide Y1 receptor (NPY1R) and anxiety-like behaviors in the hippocampi of male rat offspring exposed to maternal obesity and the potential neuroprotective effects of N-acetylcysteine (NAC). A maternal obesity model was created using a high-fat (60% k/cal) diet. NAC (150mg/kg) was administered by intragastric gavage for 25days in both the NAC and obesity + NAC (ObNAC) groups. All male rat offspring were subjected to behavioral testing on postnatal day 28, the end of the experiment. Stereological analysis was performed on hippocampal sections, while NPY1R expression was determined using immunohistochemical methods. Stereological data indicated significant decreases in the total volume of the hippocampus and CA1 and dentate gyrus (DG) regions in the obese (Ob) group (p < 0.01). Decreased NPY1R expression was observed in the Ob group hippocampus (p < 0.01). At behavioral assessments, the Ob group rats exhibited increased anxiety and less social interaction, although the ObNAC group rats exhibited stronger responses than the Ob group (p < 0.01). The study results show that NAC attenuated anxiety-like behaviors and NPY1R expression and also protected hippocampal volume against maternal obesity. The findings indicate that a decrease in NPY1R-positive neurons in the hippocampus of male rats due to maternal conditions may be associated with increased levels of anxiety and a lower hippocampal volume. Additionally, although there is no direct evidence, maintenance of NPY1R expression by NAC may be critical for regulating maternal obesity-induced anxiety-related behaviors and hippocampal structure.

Cytotoxic and antitumor properties of methionine γ-lyase conjugate in combination with S-alk(en)yl–L-cysteine sulfoxides

Background. Enzyme prodrug therapy is a promising strategy to treat solid malignancies. The utilization of two-component systems, including an enzyme and a non-toxic prodrug, to generate cytotoxic compounds directly at the surface of the tumor cell can be successful strategy in reducing the overall toxic load on the body.Aim. To determine antitumor activity of the pharmacological pair C115H methionine γ-lyase (C115H MGL) conjugated with daidzein (C115H MGL-Dz) and of S-alk(en)yl-L-cysteine sulfoxides against various types of solid tumors in vitro and in vivo.Materials. MTT-test was used to determine the cytotoxicity of C115H MGL-Dz in the presence of S-alk(en)yl-L-cysteine sulfoxides in vitro against Sw620 (colon cancer), Panc1 (pancreatic cancer), and 22Rv1 (prostate cancer). Apopto- sis induction and cell cycle alteration in 22Rv1, Sw620, and SKBR3 cell lines were studied using the Muse® Caspase-3/7 and Muse® Cell Cycle Assay kits. In vivo anticancer activity was studied on Sw620, Panc1, and 22Rv1 subcutaneous xenografts in Balb/c nude mice.Results. The C115H MGL-Dz had the maximum cytotoxic activity in the presence of S-propyl-L-cysteine sulfoxide (propiin) with IC50 values: 3.88 and 5.4 for Panc1 and 22Rv1, respectively. Dipropyl thiosulfinate formed by the β-eli-mination of propiin catalyzed by C115H MGL-Dz, induces apoptosis through both the activation of caspases and alternative pathways, and also it inhibits cell division, contributing to a decrease in the concentration of cells in the G2/M phase. The anticancer efficacy of the pharmacological pair C115H-Dz/propiin in vivo indicated a significant decrease in Panc1 tumor volume (tumor growth inhibition (TGI) 67.5 %, p = 0.004), Sw620 (TGI 22.07 %, p = 0.12) and 22Rv1 (TGI 70 %, p = 0.043).Conclusion. Pharmacological pair C115H MGL-Dz/propiin was capable of suppressing tumor development in malignant solid tumors and might be considered as a potential anticancer approach in cancer prodrug therapy.

Impact of deep learning image reconstructions (DLIR) on coronary artery calcium quantification

BackgroundDeep learning image reconstructions (DLIR) have been recently introduced as an alternative to filtered back projection (FBP) and iterative reconstruction (IR) algorithms for computed tomography (CT) image reconstruction. The aim of this study was to evaluate the effect of DLIR on image quality and quantification of coronary artery calcium (CAC) in comparison to FBP.MethodsOne hundred patients were consecutively enrolled. Image quality–associated variables (noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR)) as well as CAC-derived parameters (Agatston score, mass, and volume) were calculated from images reconstructed by using FBP and three different strengths of DLIR (low (DLIR_L), medium (DLIR_M), and high (DLIR_H)). Patients were stratified into 4 risk categories according to the Coronary Artery Calcium - Data and Reporting System (CAC-DRS) classification: 0 Agatston score (very low risk), 1–99 Agatston score (mildly increased risk), Agatston 100–299 (moderately increased risk), and ≥ 300 Agatston score (moderately-to-severely increased risk).ResultsIn comparison to standard FBP, increasing strength of DLIR was associated with a significant and progressive decrease of image noise (p < 0.001) alongside a significant and progressive increase of both SNR and CNR (p < 0.001). The use of incremental levels of DLIR was associated with a significant decrease of Agatston CAC score and CAC volume (p < 0.001), while mass score remained unchanged when compared to FBP (p = 0.232). The underestimation of Agatston CAC led to a CAC-DRS misclassification rate of 8%.ConclusionDLIR systematically underestimates Agatston CAC score. Therefore, DLIR should be used cautiously for cardiovascular risk assessment.Key Points• In coronary artery calcium imaging, the implementation of deep learning image reconstructions improves image quality, by decreasing the level of image noise.• Deep learning image reconstructions systematically underestimate Agatston coronary artery calcium score.• Deep learning image reconstructions should be used cautiously in clinical routine to measure Agatston coronary artery calcium score for cardiovascular risk assessment.

Retinal maculo‐papillary OCT and hippocampal and others cerebral areas MRI in subjects with a family history of Alzheimer's disease and allelic characterization for ApoE ɛ4

AbstractPurpose: In addition to advanced age, genetic inheritance is another predisposing factor for the development of Alzheimer's disease (AD). Retinal changes already exist in preclinical stages, so the aim of this study was to analyse possible retinal changes in subjects at high risk of developing AD using OCT and correlate them with brain areas analysed by magnetic resonance imaging (MRI).Methods: Macular and peripapillary OCT and brain MRI were performed in 64 cognitively healthy subjects. 30 controls were subjects with no family history of AD and carrying no ApoE ɛ4 allele (FH− ApoE ɛ4−), while 34 subjects had an affected first‐degree relative and at least one ɛ4 allele (FH+ ApoE ɛ4+).Results: We observed in the FH+ ApoE ɛ4+ group compared to the control group a significant volume reduction in the following macular areas: (i) macular RNFL (mRNFL), (ii) inner plexiform layer (IPL); (iii) inner nuclear layer (INL) and (iv) outer plexiform layer (OPL). Moreover, in the FH+ ApoE ɛ4+ group the retinal sectors that showed a statistically significant decrease in volume correlated with brain areas that are affected in the early stages of AD, such as the lingual gyrus, the hippocampal region and the entorhinal cortex. In the same group, no statistically significant changes in thickness were found in the peripapillary retinal nerve fibre layer (pRNFL) compared to the control group. However, correlations of these sectors with brain areas involved in this pathology were also found.Conclusions: In cognitively healthy subjects at high genetic risk of developing sporadic forms of AD, there are significant correlations between the changes observed in the retina and brain areas closely related to AD, such as the lingual gyrus, the hippocampal area and the entorhinal cortex.

Functional Recovery Measured by Longitudinal Daily Steps in Individuals with Acetabular Dysplasia Undergoing Periacetabular Osteotomy

<h3>Research Objectives</h3> Periacetabular osteotomy (PAO) is a surgical procedure for individuals with acetabular dysplasia (AD), with goals of increasing hip joint bony congruency and improving pain and function. Little is known regarding functional recovery over time following PAO. We used commercially-available wrist-worn activity trackers to monitor daily steps from before to 4 months following PAO. <h3>Design</h3> A cohort study. <h3>Setting</h3> University laboratory. <h3>Participants</h3> 6 women with AD scheduled for PAO (mean age=23.2±9.2). <h3>Interventions</h3> PAO. <h3>Main Outcome Measures</h3> We provided participants with a commercially-available smart watch (Fitbit Ionic) to wear daily from before PAO through 4-months following PAO. We linked each participant's device with an online data platform (Fitabase) designed specifically for wearable data. Following PAO, participants underwent standardized rehabilitation and started involved-limb weightbearing near 6 weeks following PAO (range: 4-12 weeks following PAO). We calculated average daily step volume before PAO, and at 2 weeks, 1 month, and 4 months following PAO. We used repeated-measures ANOVA to compare step volume at each time point before and after PAO. <h3>Results</h3> Compared to step volume before PAO (5,054±2,731 steps/day), there were significant decreases in step volume at 2 weeks following PAO (1,418±1,090 steps/day, p=.017) and at 1 month following PAO (1,525±1,365 steps/day, p=.019). There was no significant difference in step volume before PAO versus at 4 months following PAO (5,129±2,514, p=.950). <h3>Conclusions</h3> By 4 months following PAO, individuals with AD demonstrated a similar volume of daily steps as to that of baseline values. Using consumer-accessible activity trackers before and after PAO provides objective, continuous estimation of physical activity and walking data, and further study may provide real-world data to inform surgical outcomes and optimal timing of return to work/activity. <h3>Author(s) Disclosures</h3> None.

Change in cardiorespiratory fitness, hippocampal subfields and virtual navigation in older adults: a randomized controlled trial

AbstractBackgroundHippocampal neuroplasticity is oppositely affected by aging and exercise. Rodent models have demonstrated a specific exercise‐induced neuroplasticity enhancement in the dentate gyrus (DG) subfield of the hippocampus associated with improved spatial memory. In humans, exercise‐induced enhancement in cardiorespiratory fitness (CRF) has been shown to increase the left anterior DG volume among young adults. Cross‐sectional studies in older adults showed that higher CRF is associated with greater subiculum volume in women and attenuated age‐related decline in performance of hippocampus‐dependent spatial navigation tasks. However, it is unknown whether these relationships hold for exercise‐induced enhancement in CRF among older adults.MethodIn this study, 32 older adults who completed one of two randomized controlled trials (RCT; ClinicalTrials.gov; NCT02057354; NCT02775760) participated in a 12‐week moderate‐intensity, trainer‐supervised exercise training program. Participants were randomized into two groups, active control (resistance training; RT) and endurance training (ET). The aim of this RCT was to examine the effects of exercise training and training‐induced increases in CRF on hippocampal subfield volumes and activation during virtual navigation in cognitively‐healthy sedentary older adults (55‐85 years old) using structural MRI and fMRI. FreeSurfer 7.1 was used to automatically segment hippocampal subfields using T1 and high‐resolution T2‐weighted images. AFNI 19.0 was used for fMRI preprocessing and analyses.ResultOur structural MRI results demonstrated that after the 12‐week period, the RT but not the ET group showed a marginally significant volume decrease in the right anterior DG. Additionally, CRF increase was significantly associated with volume increase in the left anterior subiculum among women. Our fMRI results showed that CRF increase predicted a marginally significant lower fMRI activation in the left subiculum. Finally, an exploratory whole‐brain fMRI analysis showed that CRF increase significantly predicted lower activation in the cuneus and right inferior frontal gyrusConclusionOur results extend findings from animal models on DG neuroplasticity to older adult humans and to brain areas associated with spatial navigation. Furthermore, our results suggest that exercise and CRF may attenuate aging‐related decline in the structural and functional integrity of hippocampal subfields among older adults, especially among women, and possibly by targeting the subiculum.

Impact of transcatheter tricuspid valve replacement for tricuspid regurgitation on hepatic, cardiac, and venous structure

BackgroundPatients with long-term tricuspid regurgitation (TR) are mostly accompanied by hepatic, cardiac, and venous remodeling. Transcatheter tricuspid valve replacement (TTVR) device has emerged as a promising alternative to open-heart surgery for TR patients. No study has assessed the impact of TTVR on hepatic, cardiac, and venous remodeling. MethodsTwenty-two patients with TR enrolled in this study underwent TTVR between October 2020 and January 2021. Liver, heart, and veins were reconstructed by three-dimensional computed tomography reconstruction software at baseline and 6 months follow-up. ResultsTwenty-two patients were enrolled in this study. The mean age was 64.8 ± 8.2 years, and all patients had severe or greater TR with multiple comorbidities. The left hepatic lobe volume decreased from 518.8 ± 171.9 ml to 470.4 ± 179.6 ml at 6 months during follow-up (p = 0.049). Evidence of a decrease in three hepatic veins parameters and splenic vein parameters was noted from baseline to 6 months. And a significant decrease in right atrial volume (317.5 ml [interquartile range: 216.1 to 497.3 ml] vs. 266.7 ml [interquartile range: 178.7 to 480.7 ml]; p = 0.003) were observed in the study. ConclusionsSix-month outcomes show that TR elimination by LuX-Valve is associated with the reverse remodeling of liver, heart, and veins. Accordingly, LuX-Valve is a promising alternative for patients presenting with severe TR.

Trends in coronary calcium score and coronary CT angiography imaging volume during the COVID-19 pandemic

The COVID-19 pandemic disrupted the delivery of preventative care and management of acute diseases. This study assesses the effect of the COVID-19 pandemic on coronary calcium score and coronary CT angiography imaging volume. A single institution retrospective review of consecutive patients presenting for coronary calcium score or coronary CT angiography examinations between January 1, 2020 to January 4, 2022 was performed. The weekly volume of calcium score and coronary CT angiogram exams were compared. In total, 1,817 coronary calcium score CT and 5,895 coronary CT angiogram examinations were performed. The average weekly volume of coronary CTA and coronary calcium score CT exams decreased by up to 83% and 100%, respectively, during the COVID-19 peak period compared to baseline (P < 0.0001). The post-COVID recovery through 2020 saw weekly coronary CTA volumes rebound to 86% of baseline (P=0.024), while coronary calcium score CT volumes remained muted at only a 53% recovery (P < 0.001). In 2021, coronary CTA imaging eclipsed pre-COVID rates (P=0.012), however coronary calcium score CT volume only reached 67% of baseline (P < 0.001). A significant decrease in both coronary CTA and coronary calcium score CT volume occurred during the peak-COVID-19 period. In 2020 and 2021, coronary CTA imaging eventually superseded baseline rates, while coronary calcium score CT volumes only reached two thirds of baseline. These findings highlight the importance of resumption of screening exams and should prompt clinicians to be aware of potential undertreatment of patients with coronary artery disease.

Tumor Treating Fields (TTFields) Concomitant with Immune Checkpoint Inhibitors Are Therapeutically Effective in Non-Small Cell Lung Cancer (NSCLC) In Vivo Model.

Tumor Treating Fields (TTFields) are electric fields that exert physical forces to disrupt cellular processes critical for cancer cell viability and tumor progression. TTFields induce anti-mitotic effects through the disruption of the mitotic spindle and abnormal chromosome segregation, which trigger several forms of cell death, including immunogenic cell death (ICD). The efficacy of TTFields concomitant with anti-programmed death-1 (anti-PD-1) treatment was previously shown in vivo and is currently under clinical investigation. Here, the potential of TTFields concomitant with anti- PD-1/anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) or anti-programmed death-ligand 1 (anti-PD-L1) immune checkpoint inhibitors (ICI) to improve therapeutic efficacy was examined in lung tumor-bearing mice. Increased circulating levels of high mobility group box 1 protein (HMGB1) and elevated intratumoral levels of phosphorylated eukaryotic translation initiation factor 2α (p-eIF2α) were found in the TTFields-treated mice, indicative of ICD induction. The concomitant application of TTFields and ICI led to a significant decrease in tumor volume as compared to all other groups. In addition, significant increases in the number of tumor-infiltrating immune cells, specifically cytotoxic T-cells, were observed in the TTFields plus anti-PD-1/anti-CTLA-4 or anti-PD-L1 groups. Correspondingly, cytotoxic T-cells isolated from these tumors showed higher levels of IFN-γ production. Collectively, these results suggest that TTFields have an immunoactivating role that may be leveraged for concomitant treatment with ICI to achieve better tumor control by enhancing antitumor immunity.

Changes of sperm parameters in men recovered from coronavirus disease 2019 (covid-19): a comparison between precovid and postcovid period

The Coronavirus disease 2019 (COVID-19), which is the cause of a global pandemic, is thought to damage the male reproductive system via both direct and indirect pathways, according to several hypotheses. However, there are very limited studies in the literature examining the changes in male sperm parameters before and after COVID-19. The aim of this study is to evaluate the effect of COVID-19 on male reproductive health. The men included in the male sexual health cohort of our clinic within the last 6 months were screened, retrospectively. 25 individuals with a history of COVID-19 following the first clinical evaluation who did not have active symptoms at the present were invited to be examined in the 3rd month after COVID-19. The spermiogram parameters of the subjects in the last 6 months before COVID-19 and in the 3rd month after COVID-19 were compared. In addition, SARS CoV-2 PCR analysis was performed on semen samples of all participants. The study group had a mean age of 34.8±7.7, a mean BMI of 26.82±5.3, a Charlson comorbidity index score of 0.16±0.37, and a paternity ratio of 8/25 (32%). COVID-19 severity was mild in 19/25 (76%) of the participants and moderate in 6/25 (24%), with a mean COVID-19 duration of 9.2±5.42 days. The SARS CoV-2 PCR test was negative in the semen samples of all subjects. Although the sperm morphology did not alter, there was a statistically significant decrease in semen volume and sperm concentration, as well as progressive and total sperm motility in the postcovid period compared to the precovid period of the same subject (p<0.05; p<0.05; p<0.01; p<0.01, respectively). In males who recovered from COVID-19, all spermiogram parameters except sperm morphology were impaired. Long-term cohort studies in larger populations are required to determine whether this deterioration is permanent. The authors declare no conflict of interest.

LBSAT238 Teprotumumab Reduces Orbital Fat And Muscle Volume In Patients With Thyroid Eye Disease

Abstract Teprotumumab, a novel IGF-1R antibody has been shown to reduce proptosis in patients with thyroid eye disease (TED) in 2 randomized controlled trials. At present, it is unclear whether the reduction in proptosis is related to a decrease in extraocular muscle or orbital fat tissue. In this prospective longitudinal study, we reviewed the changes to orbital fat and muscle, and compared them, in consecutive patients with TED, who had completed treatment with teprotumumab (8 infusions). The primary outcome was change in orbital fat and muscle volume within 6 weeks of starting and completing therapy. Secondary outcome measures included change in proptosis and the clinical activity score (CAS). All patients had either CT or MRI with ≤ 1 mm slice thickness. Three-dimensional volumetric analysis of the orbital fat and muscle volume was performed using the previously validated 3D image analysis software, MIMICS (Materialise, Leuven, Belgium). Hounsfield units of fat and muscle were defined manually. All extraocular muscle tissue and fat between the orbital septum (eyelid) and the orbital outlet of the optic canal was included. A 3D model created by voxel addition was expressed in millimeters cubed. Segmentation and measurements were performed independently by two graders to review repeatability and observer variability. In line with previous clinical trials, the orbit with the most proptosis was defined as the study orbit and the contralateral orbit was designated the fellow orbit. Twenty-one patients (15 females and 6 males) met the inclusion criteria. Mean (SD) age was 55 (16), while mean (SD) duration of TED was 71 (46) months. There was a reduction of 3 mm in both; study and fellow orbits following treatment (p &amp;lt; 0. 01 for both). Compared to baseline, there was a mean (SD) CAS reduction of 4 (1) in the study orbit and 2.4 (1.1) in the fellow orbit (p &amp;lt; 0. 01 for both). Following therapy, mean (SD) reduction in muscle tissue was 1691 mm3 (1358) in the study orbit and 1714 mm3 (1927) in the fellow orbit (p &amp;lt; 0. 01 when compared to baseline for each). The mean (SD) reduction of fat volume was 1382 mm3 (1318) in the study orbit and 933 mm3 (1699) in the fellow orbit (p &amp;lt; 0. 01 when compared to baseline for each). There was no difference between fat and muscle reduction for the study orbit (p = 0.4) or fellow orbit (p = 0.2). There was a significant correlation between a reduction in proptosis and reduction in orbital soft tissue (fat and muscle) volume. The results of this study suggest that following treatment with teprotumumab, there is a significant decrease in orbital fat and muscle volume. This reduction in soft tissue volume likely drives the reduction in proptosis. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Assessment of the impact of the Dniester Hydropower Complex on hydrological state of the Dniester River

Operation of the Dniester Hydropower Complex (DHC), build on the middle course of the Dniester River in the middle of the '80s of the last century and extended during last decades, on one hand, produces low-cost energy and contributes to local and regional economical development, but on the other hand, leads to modification of river flow and ecosystems in the downstream, creating a series of dilemmas that are difficult to manage and solve by bazinal countries, Ukraine and the Republic of Moldova. This research aims to assess the changes in flow, phases of the hydrological regime, water temperature and sediments’ regime due to the DHC operation. Main utilized approach was comparative analysis of hydrological time series recorded at the stations situated upstream and downstream of the DHC, for two representative time periods: before and after construction of this hydropower complex. As a result, it was estimated that the mean annual flow downstream the DHC decreased by 9.2%. Seasonal flow changed mainly by significant decrease in February-April (February - 18%, March - 40%, April - 27%), and increase in the autumn months, by 10-14%.Minimum flows upstream of the DHC, increased by 52%, and downstream have doubled, reaching 107m3/s (compared to 51m3/s, before the DHC construction). Maximum annual flow, in the upstream part, in the second period, has slightly increased, while towards the downstream part, there is a reduction of this parameter by about 30%.One of the direct impacts of the DHC operation is hydropeaking effect. Intraday level amplitude downstream of the DHC amounts to 52 cm and the length of the sector that is influenced by this effect is over 100 km. Also, a long river sector is subject to water thermal modifications: when upstream the average annual water temperature has risen by 0.8°C, in the downstream it has diminished by 0.44°C. On a monthly scale, there is a decrease in the water temperature in the spring-summer period, and an increase in the autumn-winter period downstream of the DHC. Sediment transport process was also altered significantly. Due to the DHC operation, suspended sediments decreased by 92-98% downstream of it. The significant decrease in sediment volumes is specific to all months of the year. The reduction of sediment transport has increasedthe transparency of water, which, as a result, influences the development of the aquatic ecosystems.

Complex treatment of patients with chronic bacterial prostatitis using biologically active peptides

BACKGROUND: Increasing the effectiveness of the treatment of chronic bacterial prostatitis is an actual problem of modern urology.&#x0D; AIM: The aim of the study was to study the effectiveness of complex treatment of patients with chronic bacterial prostatitis using Prostatex.&#x0D; MATERIALS AND METHODS: This study included 94 patients with chronic bacterial prostatitis aged 21 to 45 years. Patients of group I (n = 47) received standard antibiotic therapy (levofloxacin at a dose of 500 mg 2 times a day for 28 days), and patients of group II (n = 47) received standard antibiotic therapy combined with the prescription of Prostatex in the form of rectal suppositories 10 mg once a day.&#x0D; RESULTS: The overall clinical efficacy of treatment in patients of group II was 2 times higher than in patients of group I. After treatment in patients of group II compared with group I a statistically significant decrease in chronic bacterial prostatitis symptoms according to the NIH-CPSI and IPSS questionnaires was recorded. Eradication of microflora in 91.4% of patients of group II was achieved, there was a significant decrease in prostate volume, an increase in the average volumetric flow rate of urine by 89.8%, normalization of perfusion parameters and the index of microcirculation efficiency.&#x0D; CONCLUSIONS: The results of the study showed that the use of Prostatex in the complex treatment of chronic bacterial prostatitis patients has a positive effect on the main symptoms of chronic prostatitis, significantly reducing pain, urination disorders and improving sexual function. This therapy helps to reduce the volume of the prostate and the volume of residual urine, restores microcirculation in the prostate gland and can be recommended in this category of patients.

Effectiveness of 6D couch with daily cone beam computed tomography in reducing PTV margins for glioblastoma multiforme.

Image-guided radiotherapy maximizes therapeutic index of brain irradiation by reducing setup errors during treatment. The aim of study was to analyze setup errors in the radiation treatment of glioblastoma multiforme and if decrease in planning target volume (PTV), margin is feasible using daily cone beam CT (CBCT) and 6D couch correction. Twenty-one patients (630 fractions of radiotherapy) were studied in which corrections were made in 6° of freedom. We determined setup errors, impact of setup errors of initial three fractions CBCT versus rest of the treatment with daily CBCT, and mean difference in setup errors with or without application of 6D couch and volumetric benefit of reduction of PTV margin from 0.5 cm to 0.3 cm. The mean shift in the conventional directions, namely, vertical, longitudinal, and lateral was 0.17 cm, 0.19 cm, and 0.11 cm. There was significant change in vertical shift when first three fractions were compared with rest of the treatment with daily CBCT. When the effect of 6D couch was nullified, all directions showed increased error with longitudinal shift being significant. The number of setup errors of magnitude >0.3 cm was more significant when only conventional shifts were applied as compared with 6D couch. There was significant decrease in volume of brain parenchyma irradiated when margin of PTV was reduced from 0.5 cm to 0.3 cm. Daily CBCT along with 6D couch correction can reduce setup error which allows reduction in PTV margin during radiotherapy planning in turn improving the therapeutic index.

Hyaluronic Acid Spacer in Prostate Cancer Radiotherapy: Dosimetric Effects, Spacer Stability and Long-Term GI Toxicity and PRO in a Phase II-Study

<h3>Purpose/Objective(s)</h3> Rectal side effects are common after radiotherapy (RT) to the prostate. To reduce side effects, perirectal spacers to separate the prostate from the rectum, thereby reducing the rectal dose, may be beneficial. This study presents the impact of a hyaluronic acid (HA) perirectal spacer on the rectal dose, MRI evaluation of spacer thickness during RT and a five-year follow-up of patient-reported outcome (PRO) and gastrointestinal (GI) toxicity. <h3>Materials/Methods</h3> 81 patients (<75 years) with low- (T1c-T2 and Gleason ≤ 6 and PSA < 10) and intermediate-risk prostate cancer (PC) (T1c-T3a with 1 or 2 of the risk factors T2c-T3a or Gleason ≥ 7 or PSA ≥ 10) received transrectal injections with HA (Macrolane VRF 30, Q-Med/Galderma, Uppsala, Sweden) as a perirectal spacer in this phase II-study between 2010-2016. External beam RT, 78 Gy in 39 fractions, were given with 3DCRT or IMRT using fiducial markers as image guidance. MRI was performed before (MR0) and after HA injection (MR1), at the middle (MR2) and at the end of RT (MR3). GI toxicity was assessed up to five years according to the RTOG scale. PRO GI side effects were collected using The Swedish national prostate cancer registry (NPCR) and PCSS questionnaires. <h3>Results</h3> HA thickness was measured at the prostate base, middle and apex for 52 of 81 patients. Exclusion due to failed HA-injections (6), missing MRT or RT data (17), larger PTV margins (5) and other treatment (1). HA thickness and CTV-Rectum spaces in apex- and middle- position was decreasing from MR1 to MR2/MR3. No significant differences were found between MR2 and MR3. Overall, HA thickness in the middle position had the strongest significant correlation (Spearman's rho ρ= 0.70) to CTV-Rectum spacing. There was a significant decrease in the relative rectum volume that received 70.2 Gy (V90%) from MR0 (8.6 ±5.7 %) to MR1 (2.7± 4.1 %). There was a significant increase from MR1 to MR2 (6.0±9.0%) and no significant difference between MR2 and MR3 (5.7±7.9 %) in rectum V90%. All with significance p<0.05. At the end of RT 17 patients (25.8%) experienced grade 1 GI toxicity, and four patients (6.1%) grade 2. At six months the proportion of grade 2 and 3 GI toxicity was 3.2%, and 1.6%. After 18 months no grade ≥ 2 GI toxicity was observed. The estimated cumulative late grade ≥ 2 GI toxicity rate at 5 years was 4.8 %. PRO moderate or severe overall bowel problems at start RT, end of RT and 5 years were 0%, 17.6% and 12.2% with a mean score of 14.6 (scale 0–100; higher value refers to more symptoms/worse function) at 5 years. <h3>Conclusion</h3> After HA-spacer, the relative rectum volumes receiving 70.2 Gy (V90%) were significantly lower. V90% increased significantly from MR1 to MR2/MR3, but still a significant reduction from MR0. The 5-year cumulative risk of late GI toxicity grade >1 was low whereas 12 % reported moderate/severe GI-bothers in the PRO at 5 years.