Decline In Serum Research Articles

Debulking surgery after muscular paraffin oil injections: Effects on calcium homeostasis and patient satisfaction.

Cosmetic paraffin oil injections can lead to granuloma formation causing hypercalcemia and kidney failure. This study explores whether debulking surgery is an effective treatment for improving calcium homeostasis, inflammation and clinical symptoms. In a retrospective study, we reviewed 33 patients undergoing debulking surgery. Changes in calcium, inflammatory markers, and renal function from baseline up to twelve months post-surgery were assessed. Patients were interviewed post-surgery. The patients were 34.6 years (SD 6.9) and had 1,104 grams (SD 591) of granuloma tissue removed following injection of 1,329 mL (SD 803) paraffin oil 7.9 years (SD 3.2) earlier. Seventeen patients had hypercalcemia and experienced a significant decline in ionized calcium from 1.48 mmol/L (SD 0.16) at baseline to 1.33 mmol/L (SD 0.03) at twelve months (p<0.002), although only four men (23.5%) became normocalcemic. Serum ferritin was reduced by 50% after twelve months (p=0.048). Sixteen patients were normocalcemic and had no change in calcium homeostasis but experienced a 20% drop in serum ferritin levels (p=0.025) after surgery. Fifteen patients completed all their planned surgeries within the study period and experienced a decline in serum ionized calcium (p=0.031), ferritin (p=0.011), and interleukin 2-receptor (p=0.037). A patient satisfaction survey showed that 55% of patients reported post-operative satisfaction scores of 10/10, and 59% of the patients reported reduced pain. Surgery improved calcium homeostasis in a fraction of patients, reduced inflammation and subjective symptoms such as pain and mental well-being in a patient group left with few treatment options except high-dose prednisolone.

Exosomal YB-1 facilitates ovarian restoration by MALAT1/miR-211-5p/FOXO3 axis

Premature ovarian failure (POF) affects many adult women less than 40 years of age and leads to infertility. Mesenchymal stem cells-derived small extracellular vesicles (MSCs-sEVs) are attractive candidates for ovarian function restoration and folliculogenesis for POF due to their safety and efficacy, however, the key mediator in MSCs-sEVs that modulates this response and underlying mechanisms remains elusive. Herein, we reported that YB-1 protein was markedly downregulated in vitro and in vivo models of POF induced with H2O2 and CTX respectively, accompanied by granulosa cells (GCs) senescence phenotype. Notably, BMSCs-sEVs transplantation upregulated YB-1, attenuated oxidative damage-induced cellular senescence in GCs, and significantly improved the ovarian function of POF rats, but that was reversed by YB-1 depletion. Moreover, YB-1 showed an obvious decline in serum and GCs in POF patients. Mechanistically, YB-1 as an RNA-binding protein (RBP) physically interacted with a long non-coding RNA, MALAT1, and increased its stability, further, MALAT1 acted as a competing endogenous RNA (ceRNA) to elevate FOXO3 levels by sequestering miR-211-5p to prevent its degradation, leading to repair of ovarian function. In summary, we demonstrated that BMSCs-sEVs improve ovarian function by releasing YB-1, which mediates MALAT1/miR-211-5p/FOXO3 axis regulation, providing a possible therapeutic target for patients with POF.

Changes in mucosal IgG4+- and IL-10+-cell frequencies in adults with eosinophilic esophagitis on a two-food elimination diet

Eosinophilic esophagitis (EoE) is increasingly diagnosed in patients with dysphagia. Type-2 immunity can induce EoE histopathology via non-IgE-dependent mechanisms, possibly involving IgG4 and IL-10. To elucidate the contribution of this response to EoE pathogenesis, we examined its association with clinical and histologic endpoints in adult EoE patients given a two-food elimination diet. IgG4- and IL-10-expressing cells were counted in esophageal biopsies and serum food-specific IgG4 measured at baseline and follow-up. Variables were correlated with histologic measures of disease activity. Patients exhibited significant reduction in esophageal eosinophilia and overall histology. A significant decrease in IL-10+-cell frequencies correlated with histologic changes. In contrast, a decline in serum and esophageal IgG4, while substantial, did not correlate with IL-10+-cell frequencies or histologic parameters. These results suggest a critical role of IL-10 in EoE pathogenesis. Conversely, IgG4 expression, while reflecting exposure to food antigens, is not obviously related to EoE histopathology or IL-10 expression.

OR04-05 Prenatal Phthalate Exposure Alters The Pattern Of Fetal And Neonatal Endocrine Puberty In A Sex-specific Manner

Abstract Disclosure: M.A. Bunnell: None. P. Lin: None. S. Zhou: None. C. Park: None. S. Wang: None. Q. Hu: None. B. Marzbanabbasabadi: None. J. Oh: None. B. Wang: None. M. Laws: None. E. Fletcher: None. Z. Liu: None. E. Joo: None. H. Qiao: None. J. Flaws: None. C. Ko: None. Endocrine puberties (EP) are sex-specific transient elevations of gonadotropins and testosterone (T) in males and estradiol (E2) in females. Fetal EP occurs mid-gestation, neonatal EP is stimulated by the clearance of maternal estrogen after birth, and finally, reproductive function arises during classical puberty. EPs are critical for normal development and the sexual dimorphism of reproductive and some somatic organs. Disrupted T or E2 levels during fetal or neonatal EP lead to reproductive abnormalities in adults. The endocrine disrupting effects of phthalates have been well-documented in humans and animal models. Prepubescent children are highly susceptible to phthalate toxicity. In utero, exposure to phthalates causes gender-specific reproductive abnormalities. In this study, we tested the working hypothesis that in utero exposure to phthalates alters T and E2 levels in fetal and newborn mice in a gender-specific manner. Pregnant CD-1 dams (n=5-6/treatment/time point) were orally administered an environmentally relevant phthalate mixture (20 μg/Kg/day) or vehicle daily from embryonic day (ED) 10.5 until birth. On ED16.5, and postnatal hours (h) 1, 3, and 6, fetal tissues and neonatal sera and tissues were sampled for hormonal assays. Fetal and neonatal gonads were collected for testicular T and ovarian E2 measurements. The amount of serum per embryo was insufficient for determining circulating hormone levels in the fetus. Hence, at ED16.5, hormonal content of the full-body (excluding gonads) was used to assess the impact of phthalate exposure. Hormone levels were quantified by ELISA. At ED16.5, full-body T level was lower in exposed females (2.93 vs. 12.23 pg/body in control, P&amp;lt;0.0001), but higher in exposed males (277 vs. 216 pg/body in control, P=0.022). However, there was no difference in fetal testicular T (871 vs. 1027 pg/2 testes in control, P=0.089), indicating that testicular steroidogenesis was unaltered. A rapid decline in serum T levels occurred in both newborn control (h1= 623 pg/mL, h6= 249 pg/mL, P=0.009) and exposed males (h1= 600 pg/mL, h6= 224 pg/mL, P=0.0015), but serum LH remained constant (Control: h1= 0.83 ng/mL, h6= 0.63 ng/mL, P=0.36; exposed: h1= 0.69 ng/mL, h6= 0.82 ng/mL, P=0.43). Phthalate exposure did not impact neonatal serum T or LH in males. However, at h6, exposed females had lower serum E2 than controls (0.7 vs. 8.51 pg/mL in control, P=0.001). This study found that prenatal phthalate exposure altered T and E2 levels of males and females distinctly, without disrupting LH secretion and gonadal steroidogenesis. The results indicate that T and E2 levels were likely disrupted by altered steroid clearance due to a sex-dependent impact on hepatic T and E2 metabolism, rather than pituitary or gonadal hormone production. In conclusion, prenatal exposure to a phthalate mixture alters the levels of T and E2 during fetal and neonatal EP in a gender-specific manner. Presentation: Thursday, June 15, 2023

Changes in the Eicosapentaenoic Acid to Arachidonic Acid Ratio in Serum over 10 Years in a Japanese Community: The Hisayama Study.

Circulating omega-3 and omega-6 polyunsaturated fatty acids may to contribute to cardiovascular health at the population level. Over a decade, we investigated changes in the serum eicosapentaenoic acid (EPA) to arachidonic acid (AA) ratio, and in serum concentrations of the individual fatty acids, in a Japanese community. Community surveys took place in 2002-2003 and 2012-2013 in a rural area of Japan. The community surveys included 3,194 and 3,220 community dwellers aged ≥ 40 years who did not take EPA medication in 2002-2003 and 2012-2013, respectively. Fatty acid fractionations in serum were measured using a gas chromatography method. Changes in the serum EPA/AA ratio over time were examined using linear mixed models. Overall, the average serum EPA/AA ratio decreased over the 10 years. A decreasing trend in the serum EPA/AA ratio occurred in all age groups except participants aged ≥ 80 years, with larger decreases in the younger age groups. A similar decline in serum EPA/AA ratio occurred in participants with and those without lipid-lowering therapy. Serum EPA concentrations were slightly increased in the whole population but remained stable or even decreased in participants aged 40-69. In contrast, the average serum AA concentrations increased in all age groups. In a Japanese community, the serum EPA/AA ratio decreased over 10 years at the population level, especially in middle-aged participants.

Mitigating the Denosumab-Induced Rebound Phenomenon with Alternating Short- and Long-Acting Anti-resorptive Therapy in a Young Boy with Severe OI Type VI.

Osteogenesis imperfecta (OI) type VI, a recessively inherited form of OI caused by mutations in SERPINF1, is a severe form distinguished by osteomalacia on bone histomorphometry. We describe a boy with severe OI type VI who was initially treated with intravenous (IV) zoledronic acid (ZA) at 1.4years of age; however, a year later he transitioned to denosumab 1mg/kg sub-cutaneously every three months in an effort to decrease fracture rates. After two years on denosumab, he presented with symptomatic hypercalcemia due to the denosumab-induced, hyper-resorptive rebound phenomenon. Laboratory parameters at the time of the rebound were as follows: elevated serum ionized calcium (1.62mmol/L, N 1.16-1.36), elevated serum creatinine due to hypercalcemia-induced muscle catabolism (83µmol/L, N 9-55), and suppressed parathyroid hormone (PTH) (< 0.7pmol/L, N 1.3-5.8). The hypercalcemia was responsive to low-dose IV pamidronate, with a rapid decline in serum ionized calcium, and otherwise normalization of the aforementioned parameters within 10days. To benefit from the powerful, albeit short-term, anti-resorptive effect of denosumab without further rebound episodes, he was treated thereafter with denosumab 1mg/kg alternating every three months with IV ZA 0.025mg/kg. Five years later, he remained on dual alternating anti-resorptive therapy without further rebound episodes, and an overall improvement in his clinical status. This novel pharmacological approach of alternating short- and long-term anti-resorptive therapy every three months has not previously been described. Our report suggests this strategy may be an effective method for prevention of the rebound phenomenon in select children for whom denosumab may be beneficial.

Role of Oral versus Intravenous Calcium Supplementation in Plateletpheresis Donors: A Prospective Observational Study

Introduction: Single Donor Platelets (SDP) are in high demand and are the preferred choice for patients requiring recurrent platelet transfusions. Citrate, being the anticoagulant of choice, may result in symptoms of citrate toxicity due to repeated frequent donations or increased procedure time. Aim: The present study aimed to evaluate the role of prophylactic calcium supplementation (oral vs intravenous) on plateletpheresis donors and correlate their effects with adverse donor reactions (citrate toxicity). Materials and Methods: This prospective observational study on plateletpheresis donors was conducted for a period of one year in the Department of Transfusion Medicine at Government Royapettah Hospital, The Tamil Nadu Dr. MGR Medical University, Chennai, India. It included 63 plateletpheresis donors divided into two groups based on random allocation-the Oral calcium supplementation group (n=32 donors) and the intravenous calcium supplementation group (n=31 donors). For both groups, their biochemical parameters (serum calcium, serum ionised calcium, serum magnesium) were measured before and within 30 minutes after the plateletpheresis procedure. The parameters were analysed for symptoms of citrate toxicity. Analysis was carried out using Statistical Package for Social Sciences (SPSS) Software version 20.0, and paired t-test was used for analysing biochemical parameters. Results: A statistically significant decline in serum ionised calcium levels (1.17±0.09 vs 1.10±0.11) (preprocedure level vs postprocedure level) was observed in the oral calcium supplementation group compared to the intravenous calcium supplementation group (1.07±0.25 vs 1.11±0.14). The authors observed a decline in the mean levels of serum calcium in both the oral calcium group (10.33±1.62 vs 9.88±1.00) and the intravenous calcium group (10.31±1.33 vs 10.21±0.88). Furthermore, the authors observed a decline in mean serum magnesium levels in the oral calcium group (2.13±0.30 vs 2.07±0.24) with no difference observed in the intravenous calcium group (2.14±0.22 vs 2.14±0.14). Mild citrate toxicity symptoms in the form of tingling sensation and perioral paraesthesia were observed in 26 out of 32 donors in the oral calcium group, whereas no symptoms were recorded in the intravenous calcium group. Conclusion: Prophylactic intravenous calcium supplementation resulted in better bioavailability of serum ionised calcium levels with no citrate toxicity symptoms compared to oral calcium supplementation. This results in better retention of plateletpheresis donors, enabling smooth and comfortable collection of a high concentration of platelets from a single donor. However, it is imperative to conduct more studies with a larger number of plateletpheresis donors to observe donor adverse reactions specific to the population.

Prevalence of Testosterone Deficiency in Elderly Male and its Association with Frailty and Mobility at a Tertiary Care Centre.

Background and Objectives:Several cross-sectional and prospective longitudinal studies have shown a progressive decline in Serum (S) Testosterone levels with an increase in age. The clinical consequence of this decline in S Testosterone is not clear from the prevailing data. Several ageing features like decreased libido, Osteo-sarcopenia, anemia, and depressed mood may be associated with reduced androgen levels in elderly males. This study was aimed to study the prevalence of androgen deficiency in elderly males more than 60 years of age presenting to the outpatient department of a tertiary care hospital and its association with frailty and mobility.Methods:A cross-sectional observational study was conducted over two years at a tertiary care hospital in Pune, India. The participants underwent a detailed history and physical examination. Biochemical tests and S total testosterone estimation was done. Mobility was estimated by calculating the time taken to perform the Timed Up and Go test (TUGT). Frailty was calculated by Fried's frailty index. Data are presented as mean ± standard deviation, and a comparison between the groups was made using Mann–Whitney U-test. The categorical variables are presented in frequencies along with respective percentages and were compared using the Chi-square or Fisher's exact test. The data was analyzed using SPSS version 22. A P <.05 was considered statistically significant in all the tests.Results:The mean age of the study participants was 68.37 ± 6.3 years, with a range of 60-88 years. The mean S total testosterone levels were 3.95 ± 2.06 ng/ml with a range of 0.04–25.36 ng/ml. As per the study definition, Ninety-two (21.67%) participants had testosterone deficiency. Three hundred and thirty-three (78.5%) participants had impaired motility represented by a TUGT time of more than 12 seconds. The Frailty index calculated revealed 94 (22.2%) of the study participants to be normal, 263 (62%) to be vulnerable, and 67 (15.8%) of the patients to be frail.Conclusion:The prevalence of testosterone deficiency in the elderly male population was 21.67%. However, there was no association of testosterone deficiency with frailty or impaired mobility. Furthermore, testosterone deficiency was not associated with BMI and hemoglobin levels. In the elderly, testosterone deficiency is associated with low bone mass and therefore imply an increased risk of osteoporotic fractures.

Age-related trabecular bone loss is associated with a decline in serum Galectin-1 level

BackgroundSenile osteoporosis with age-related bone loss is diagnosed depending on radiographic changes of bone and bone mineral density (BMD) measurement. However, radiographic alterations are usually signs of medium-late stage osteoporosis. Therefore, biomarkers have been proposed as indicators of bone loss. In the current study, Galectin-1 (Gal-1) showed age-related decline in mice serum. The role of Gal-1 in osteoporosis has not been investigated so far. Hence, the current study illustrated the relationship of serum Gal-1 level with bone loss.MethodsWe employed 6- and 18-month-old mice to establish an animal model of age-related trabecular bone loss, whose bone density and microstructure were investigated by micro-CT. ELISA was used to measure the levels of Gal-1 in serum. The correlation analysis was performed to illustrate the relationship between serum Gal-1 levels and trabecular bone loss. In addition, immunohistochemistry was used to investigate the abundance of Gal-1 in bone marrow of mice. ELISA and western blot were performed to measure the secretion ability and protein expression of Gal-1 in bone marrow stromal cells (BMSC), hematopoietic stem cells (HSC) and myeloid progenitor (MP) respectively. Flow cytometry was used to measure BMSC number in bone marrow. Finally, male volunteers with age-related BMD decrease were recruited and the relationship between serum Gal-1 and BMD was analyzed.ResultsGal-1 showed age-related decline in mice serum. Serum Gal-1 was positively associated with BV/TV of femur, tibia and L1 vertebrae in mice. BMSC secreted more Gal-1 compared with HSC and MP. BMSC number in bone marrow was significantly lower in aged mice compared with young mice. Significant attenuation of Gal-1 protein expression was observed in BMSC and HSC from aged mice compared with young mice. Further, we found a decline in serum Gal-1 levels in men with age-related BMD decrease. There was positive correlation between BMD and serum Gal-1 levels in these men.ConclusionsAge-related trabecular bone loss is associated with a decline in serum Gal-1 level in mice and men. Our study suggested Gal-1 had great potential to be a biomarker for discovering BMSC senescence, diagnosing early osteoporosis and monitoring trabecular bone loss.

Decline in serum progastrin-releasing peptide predicts the response of patients with small cell lung cancer to chemotherapy.

The utility of serum progastrin-releasing peptide (ProGRP) and neuron-specific enolase (NSE) as biomarkers for treatment monitoring and as prognostic factors was investigated in small cell lung cancer (SCLC) patients. Patients were first diagnosed pathologically at the First Affiliated Hospital of the University of Science and Technology of China and had their serum ProGRP and NSE levels measured using an electrochemiluminescence immunoassay. A total of 120 SCLC patients were enrolled. In responsive patients, ProGRP levels decreased significantly following two cycles of chemotherapy and continued to decline over the course of treatment. However, this decrease in ProGRP levels was not observed in non-responsive patients. Changes in ProGRP levels were more accurate than changes in NSE levels for monitoring the effects of chemotherapy in patients with SCLC. Following two treatment cycles or after the occurrence of drug resistance, changes in ProGRP levels in patients with low ProGRP levels at the time of diagnosis were not notably, regardless of whether or not patients were responders. The area under the receiver operating characteristic curve of the decline in ProGRP levels as a therapeutic biomarker of SCLC was 0.9643, and the cut-off value was 55.02%. A decline in ProGRP levels maybe a good predictor of objective response to chemotherapy in patients with SCLC with higher ProGRP levels at diagnosis. This model is expected to replace or be combined with imaging to predict chemotherapeutic treatment effects in patients with SCLC.

Effect of Cupping (Al-Hijima) on Hematological and Biochemical Parameters for some Volunteers in Missan Province

Objective: The aim of Cupping is to extract the blood which is believed to be harmful for the body which in turn rids the body of potential harm from symptoms leading to a reduction in stressful condition. The study was performed to evaluate the effects of cupping (Hijama) on the hematological and the biochemical parameters in the patients before and after making the cupping. Subjects and Method: The study was performed in period between (first November -2018 to May- 2019) and conducted on (30) volunteers coming to Hijama centers in different parts of Missan province in ages between (30-50) years with . Five (5ml) of venous blood samples were collected the first sample was taken before and after one week of cupping and two weeks later after cupping . Each sample of blood was separated into two tubes for hematological assessment and the serum was stored in -20°C freezer till handled for biochemical analysis ,determined lipid profile and serum electrolytes level. These parameters were performed in laboratories of Al- Sadder Teaching Hospital – Amarha City according to the standard methods that described in the Analysis Kits that used in this study was products of Spinach Company Spin react. Results: The obtained results for hematological analysis observed significant increase in (RBCs) after one and two week of making Hijima in (p< 0.05).as compared results before making hijjama ,significant decrease in haematocrit(HCT) ,hemoglobin (Hb) ,Platelets (Plt) , neutrophiles and lymphocytes percentages after one and two week of making Hijama as compared results before making hijama . Total cholesterol were observed significant decrease in (P>0.05) after one and two weeks of hijima in compared with the total cholesterol before making the hijima ,decrease in (LDL), (vLDL) and Triglyceride after one week and two week of hijima as compared before making the hijima .High density lipoprotein (HDL-ch) observed significant increase in (P>0.05) after one week and two weeks of making hijima as compared with (HDL ch) before making the hijima. The biochemical analysis observed significant decrease in levels of ALP enzyme,creatinine ,blood urea nitrogen and blood glucose in(P>0.05) after one and two weeks of Hijima, significant increase in levels of total proteins , AST and ALT in(P>0.05) after one and two weeks of making Al-hijima as compared with levels before making the hijima. Serum electrolytes level showed an significant decline in serum Calcium ions (Ca+2) in (P>0.05) after one and two weeks of making Al-hijima as compared to the serum calcium level before making of Al- hijama. Also observed insignificant decline in serum sodium(Na+2), chloride ions (Cl-) and potassium ions(K+) as compared to level of sodium ,chloride and potassium ions before making of Al- hijama.

Ultrasound-guided local methotrexate treatment for cesarean scar pregnancy in the first trimester: 12 years of single-center experience in China

ObjectiveTo investigate the efficacy and safety of ultrasound-guided local injection of methotrexate (MTX) in the treatment of cesarean scar pregnancy (CSP) diagnosed in the first trimester. Study designThe clinical and imaging data of 101 CSP patients who received ultrasound-guided local injection of MTX in our hospital between January 2007 and December 2018 were retrospectively analyzed. The decline in serum β human chorionic gonadotropin (βHCG) level, size and blood flow of lesions, vaginal bleeding, liver/kidney functions, and other indicators were observed or tested after treatment on a weekly basis. ResultsThe duration of amenorrhea was 6.1 ± 0.8 weeks (range: 5.7–8.1 weeks) and the initial serum βHCG level was 20,321 ± 965 U/L in 97 patients, The mean time t to βHCG normalization was 40 ± 14 days (range: 21–140 days), Minor intermittent vaginal bleeding occurred after local MTX injection, lasting 25 ± 17 days (range: 10–61 days), and the lesions at the scar sites had completely disappeared with an average interval of 39 ± 29 days ; The treatment failed in four patients. The average duration of amenorrhea was 7.5 weeks and the average initial serum βHCG level was 91,359 U/L. ConclusionUltrasound-guided local injection of MTX is an effective and minimally invasive treatment for CSP. However, it is not feasible for patients with long-term amenorrhea (>8 weeks) and markedly increased blood βHCG level.

Relationship of Glutamine, Arginine, and the Area Postrema: A Protective Anorectic Mechanism in Critical Illness? (P12-031-19)

ObjectivesPlasma Arginine (Arg) and Glutamine (Gln) are often depleted in early acute illness and sepsis. Treatment methods involving supplementation with one or both amino acids continue to be evaluated for merit. Both Arg and Gln have strong effects on the Area Postrema(AP), a highly vascularized medullary region controlling appetite and nutrient-regulated autophagy. It is plausible that Arg/Gln depletion, observed in acute illness, is a normal physiological sequestration and that supplementation in conjunction with non-protein energy intake (NPEI) counteracts these adaptive responses and healing mechanisms. This study examines the current evidence regarding energy intake and Arg/Gln provision in early critical illness. MethodsComprehensive review of in vitro, murine, and human interventional studies involving AP lesioning, Arg/Gln turnover measures, and effects of Arg/Glnprovision in acute illness. ResultsSerum Arg/Gln were negatively associated with severity of illness in murine and human studies. In vivoand murine models suggest Arg/Gln contribute to a nutrient-sensing anorectic intracellular relationship with the APduring acute stress. Associated elevations of cytokines TNFα and NF-kB lead to cellular uptake of Arg/Gln, with plasma concentrations of Arg/Gln modulating AP-mediated anorexia. To date, no clinical studies have examined this plausible relationship between nutrition support and AP feedback mechanisms. Human studies, however, have shown that total protein provision, but not Arg/Glnsupplementation, in early critical illness upregulates autophagy and benefits clinical outcomes. ConclusionsStrong evidence suggests that illness-associated anorexia and the decline in serum Arg/Gln serve as mediators in autophagy and in stimulating repair pathways. The AP appears to regulate these processes and may be negatively impacted by supplementation ofArg/Gln and increased NPEI. Further examination is needed to elucidate the AP-regulated nutrient-sensing appetite mechanisms and the potential effects of total protein intake versus specific amino acids. The labile nature of serum Arg/Glnin acute illness represents a potentially misguided and incomplete point of consideration for stress-state physiology and medical nutrition therapy. Funding Sourcesnone.

SUPPLEMENTAL VITAMIN D FOR PREVENTION OF BONE STRESS INJURIES IN COLLEGIATE ATHLETES

Purpose: Vitamin D functions to regulate serum calcium concentrations via several cellular pathways. It has also been demonstrated to affect bone mineralization and turnover, thus making it essential for skeletal strength and adaptation to mechanical stress. Stress fractures are common athletic injuries formed by cyclic, repetitive skeletal loading that causes physical breakdown of the bone’s microstructure. Excessive running or jumping, coinciding with additional factors such as malnutrition or decreased sun exposure, may elevate an athlete’s risk for sustaining this overuse injury. Serum 25(OH)D is used as a clinical marker for vitamin D status. Previous research suggests adequate vitamin D status is important for prevention of skeletal injuries. Our hypothesis states that supplemental vitamin D will normalize athletes’ vitamin D status and will reduce stress fracture injury incidence rates for elite division 1 athletes. Methods: Prospective 245 subjects were recruited from 17 sports teams at the university. All subjects were over 18 years of age. No subjects were excluded. Subject 25(OH)D status was determined twice; once in August 2016, and again in February 2017. Following each testing cycle, subjects with 25(OH)D levels below 70 ng/ml were supplemented with cholecalciferol (50,000 IU) once a week for 8 weeks. Subjects were then monitored throughout their respective sporting seasons for stress fractures or other overuse skeletal injuries. Subjects initially completed an anthropometric questionnaire, and two compliance questionnaires were to be completed following each 8-week supplementation period. Retrospective: Athlete injury reports from each of the 17 teams will be used as a control to determine the incidence of stress fractures during the 2011-2015 seasons among non-supplemented athletes. Results: 245 subjects had 25(OH)D levels tested in August (40.4?14.3 ng/ml) with 18% being insufficient or deficient (&lt;30 ng/ml). 191 subjects were tested in February (27.7?8.85 ng/ml) with 65% being insufficient or deficient, a significant decrease. All but three teams had significantly lower 25(OH)D levels in February compared to August. There was no significant difference between male and female athletes, however both groups saw significant declines in February. There was no significant difference between indoor and outdoor sports in August and February. 2 stress injuries were diagnosed in 118 enrolled subjects in our previous arm (1.65%). 2 additional stress injuries were diagnosed in 191 remaining subjects in our current arm (1.0%). 36 stress fractures were diagnosed in 571 subjects retrospectively (6.3%). Conclusion: Several factors have been shown to influence vitamin D status, including nutrition and sun exposure. Serum 25(OH)D status is expected to decline naturally in winter months due to lack of sun exposure. Results indicate a substantial decline in serum 25(OH)D from August to February in our cohort. This supports the notion that continued supplementation may be necessary to maintain appropriate vitamin D levels. The incidence of stress fractures per year as well as the proportion of stress fractures per academic year have consistently declined as more attention is paid toward vitamin D supplementation.

Amelioration of the therapeutic efficacy of 5-Flurouracil loaded chitosan nanoparticles in experimentally induced Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the most common type of liver cancer. The most important risk factor for the development of HCC is cirrhosis regardless of etiology. 5-Fluorouracil (5-FU) is widely used in the treatment of cancer. Drug resistance remains a significant limitation to the clinical use of 5-FU. The present study aimed to evaluate the therapeutic efficacy of 5-FU loaded chitosan nanoparticles in experimentally induced HCC. To achieve our purpose, one hundred and five male Swiss Albino mice were divided randomly into two major groups: Group A: comprised 25 mice served as normal control, Group B: comprised 80 mice received a daily oral dose of 0.06% DAB (165 mg/kg body.wt.) for 30 days after which the water was replaced with 0.05% aqueous solution of Phenobarbital (PB). Five chosen mice randomly from groups A and B at the time intervals 15, 30, 45 and 60 days were sacrificed to follow up with the development of HCC by biochemical and histopathological examination. Animals of group B were divided into 3 groups Group I: included 20 mice served as an untreated group, group II: included 20 mice injected intraperitoneally with 5-FU only (40mg/kg body.wt) every 2 days for 16 days, group III: included 20 mice injected intraperitoneally with 5-FU Cs NPs. Each group was further divided into two subgroups 10 mice each, one subgroup treated with ultrasonic waves; meanwhile the other subgroup without ultrasonic waves exposure. At the end of the experiment, animals were sacrified, serum ALT, hepatic ALT, and hepatic MDA were estimated; HCC was histopathologically monitored in all studied groups. There was 276.5%, 145.7%and 438.5% increase in serum ALT, hepatic ALT and hepatic MDA levels respectively comparing to the corresponding control. Liver tumors that ultimately became neoplastic were produced after 45 days. US exposure triggered a significant decline in serum and hepatic ALT activity (P = 0.001) and in hepatic MDA (P = 0.009) within 5-FU loaded Cs NPs group. Moreover, tumor growth delay and more enhanced correction in hepatic architecture was obtained by a combination of US and 5-FU loaded Cs NPs therapy. Based on these results, we can conclude that the use of 5-FU loaded chitosan nanoparticles in combination with low-intensity ultrasound ameliorates the efficacy of 5-FU as anticancer therapy for HCC.

Monitoring treatment response in chronic pulmonary aspergillosis: role of clinical, spirometric and immunological markers

ObjectivesThe treatment response in chronic pulmonary aspergillosis (CPA) is usually assessed based on the improvement in clinical and imaging findings. Herein, we evaluate serum Aspergillus fumigatus-specific IgG, serum galactomannan, weight change, and lung function for assessing treatment response in subjects with CPA. MethodsWe categorized treatment response as favourable (improved or stable clinical response with radiologically improved or stable disease) or unfavourable (worsening of symptoms or radiological progression) after 6 months of treatment with antifungal azoles. We measured A. fumigatus-specific IgG, serum galactomannan, weight, and lung function at baseline, 3 months, and 6 months in those with favourable and unfavourable treatment response. ResultsOne hundred and twenty-six consecutive treatment-naïve subjects (53.2% (67/126) males; mean ± SD age, 42.3 ± 14.7 years) with CPA were included. One hundred and six and 20 were classified as having favourable and unfavourable response, respectively. After 6 months of treatment, the decline in serum A. fumigatus-specific IgG (n = 119) was similar in those with favourable or unfavourable response (mean ± SD, -26.3 ± 45.5 mgA/L vs. –3.4 ± 65.6 mgA/L; p 0.20). There was no significant change in the serum galactomannan (favourable vs. unfavourable: mean ± SD, –0.11 ± 2.8 vs. -0.62 ± 2; p 0.92) or FEV1 (favourable vs. unfavourable: mean ± SD, 24 ± 250 mL vs. –62 ± 154 mL; p 0.19) after 6 months of treatment. There was significant loss of weight (mean ± SD, –2.5 ± 4.5 kg) in subjects with unfavourable response. ConclusionSerum A. fumigatus-specific IgG and serum galactomannan inconsistently decrease following treatment and may not be useful indicators for monitoring treatment response in CPA. Similarly, there is little change in pulmonary function following treatment. A gain in body weight is seen in those with favourable response.

Winter Cholecalciferol Supplementation at 55°N Has No Effect on Markers of Cardiometabolic Risk in Healthy Children Aged 4–8 Years

Low serum 25-hydroxyvitamin D [25(OH)D] has been associated with unfavorable cardiometabolic risk profiles in many observational studies in children, but very few randomized controlled trials have investigated this. We explored the effect of winter-time cholecalciferol (vitamin D3) supplementation on cardiometabolic risk markers in young, white, 4- to 8-y-old healthy Danish children (55°N) as part of the pan-European ODIN project. In the ODIN Junior double-blind, placebo-controlled, dose-response trial, 119 children (mean ± SD age: 6.7±1.5 y; 36% male; 82% normal weight) were randomly allocated to 0, 10 or 20 µg/d of vitamin D3 for 20 wk (October-March). Cardiometabolic risk markers including BMI-for-age z score (BMIz), waist circumference, systolic and diastolic blood pressure, serum triglycerides and cholesterol (total, LDL, HDL, and total:HDL), plasma glucose and insulin, and whole-blood glycated hemoglobin were measured at baseline and endpoint as secondary outcomes together with serum 25(OH)D. Intervention effects were evaluated in linear regression models as between-group differences at endpoint adjusted for baseline value of the outcome, and additionally for age, sex, baseline serum 25(OH)D, BMIz, time since breakfast, and breakfast content. Mean±SD serum 25(OH)D was 56.7±12.3 nmol/L at baseline and differed between groups at endpoint with concentrations of 31.1±7.5, 61.8±10.6, and 75.8±11.5 nmol/L in the 0-, 10-, and 20 µg/d groups, respectively (P<0.0001). Vitamin D3 supplementation had no effect on any of the cardiometabolic risk markers in analyses adjusted for baseline value of the outcome (all P≥0.05), and additional covariate adjustment did not change the results notably. Preventing the winter decline in serum 25(OH)D with daily vitamin D3 supplementation of 10 or 20 µg had no cardiometabolic effects in healthy 4- to 8-y-old Danish children. This trial was registered at www.clinicaltrials.gov as NCT02145195.

Low cytomegalovirus seroprevalence in early multiple sclerosis: a case for the 'hygiene hypothesis'?

Cytomegalovirus (CMV) infection has recently been associated with a lower multiple sclerosis (MS) susceptibility, although it remains controversial whether it has a protective role or is merely an epiphenomenon related to westernization and early-life viral infections. We aimed to evaluate whether CMV serostatus may differ in patients with early MS as compared with patients with non-early MS, analyzing the putative association of this virus with MS clinical course and humoral immune responses against other herpesviruses. Multicentric analysis was undertaken of 310 patients with MS (early MS, disease duration ≤5years, n=127) and controls (n=155), evaluating specific humoral responses to CMV, Epstein-Barr virus and human herpesvirus-6, as well as T-cell and natural killer (NK)-cell immunophenotypes. Cytomegalovirus seroprevalence in early MS was lower than in non-early MS or controls (P<0.01), being independently associated with disease duration (odds ratio, 1.04; 95% confidence interval, 1.01-1.08, P<0.05). CMV+ patients with MS displayed increased proportions of differentiated T-cells (CD27-CD28-, CD57+, LILRB1+) and NKG2C+ NK-cells, which were associated with a lower disability in early MS (P<0.05). CMV+ patients with early MS had an age-related decline in serum anti-EBNA-1 antibodies (P<0.01), but no CMV-related differences in anti-human herpesvirus-6 humoral responses. Low CMV seroprevalence was observed in patients with early MS. Modification of MS risk attributed to CMV might be related to the induction of differentiated T-cell and NK-cell subsets and/or modulation of Epstein-Barr virus-specific immune responses at early stages of the disease.

Winter vitamin D3 supplementation does not increase muscle strength, but modulates the IGF-axis in young children.

To explore whether muscle strength, the insulin-like growth factor axis (IGF-axis), height, and body composition were associated with serum 25-hydroxyvitamin D [25(OH)D] and affected by winter vitamin D supplementation in healthy children, and furthermore to explore potential sex differences. We performed a double-blind, placebo-controlled, dose-response winter trial at 55ºN. A total of 117 children aged 4-8years were randomly assigned to either placebo, 10, or 20µg/day of vitamin D3 for 20 weeks. At baseline and endpoint, we measured muscle strength with handgrip dynamometer, fat mass index (FMI), fat free mass index (FFMI), height, plasma IGF-1, IGF-binding protein 3 (IGFBP-3), and serum 25(OH)D. At baseline, serum 25(OH)D was positively associated with muscle strength, FFMI, and IGFBP-3 in girls only (all p < 0.01). At endpoint, baseline-adjusted muscle strength, FMI and FFMI did not differ between intervention groups. However, baseline-adjusted IGF-1 and IGFBP-3 were higher after 20µg/day compared to placebo (p = 0.043 and p = 0.006, respectively) and IGFBP-3 was also higher after 20µg/day compared to 10µg/day (p = 0.011). Children tended to be taller after 20µg/day compared to placebo (p = 0.064). No sex interactions were seen at endpoint. Avoiding the winter-related decline in serum 25(OH)D may influence IGF-1 and IGFBP-3 in children. Larger trials are required to confirm these effects, and the long-term implication for linear growth.

Management of persistent caesarean scar pregnancy after curettage treatment failure

BackgroundCaesarean scar pregnancy (CSP) is a late serious complication of caesarean section. The incidence of CSP has increased worldwide in recent years. Early diagnosis and prompt therapy are crucial to avoid catastrophic complications. There are various strategies for CSP treatment, but there is no consensus on the best management for CSP. Dilation and curettage (D&C) and hysteroscopy are common and effective treatments with their advantages and disadvantages. No in-depth study of the clinical effects of hysteroscopic management of CSP after D&C treatment failure has been conducted. The purpose of this study is to evaluate the effectiveness and safety of hysteroscopic removal of residual CSP tissue (persistent CSP) as a rescue after failed D&C management.MethodsThis is a retrospective clinical research study. Forty-five patients underwent operative hysteroscopy to remove the residual gestational tissue in the caesarean scar after failed D&C treatment. The clinical characteristics and outcomes of hysteroscopic surgeries of 45 CSP cases were investigated. All data analyses were conducted with SPSS 17.0.ResultsForty-three CSP cases after unsuccessful curettage treatment were successfully treated by operative hysteroscopy. The estimated intraoperative blood loss was 20.00 (10.00–500.00) mL, the hysteroscopic operating time was 20.00 (15.00–45.00) min, the decline of serum β-hCG the day after surgery was 71.91 ± 14.05%, the total hospitalisation time was 7.87 ± 2.26 days, the medical cost was 13,682.71 ± 3553.77 China Yuan (CNY), the time of bleeding after surgery was 7.42 ± 2.48 days, and the time of serum β-hCG resolution after surgery was 13.84 ± 9.83 days. Follow-up after discharge demonstrated that there were no severe complications for any patients.ConclusionsHysteroscopy therapy could treat persistent CSP effectively and safely after curettage treatment failure. Therapy should be individualised, and the risks and cost of the hysteroscopy procedure and anaesthesia must be considered and fully discussed with the patients before surgery.