The Effects of Gonadotropin Replacement Therapy on Metabolic Parameters and Body Composition in Men with Idiopathic Hypogonadotropic Hypogonadism.

Testosterone replacement therapy (TRT) in idiopathic hypogonadotrophic hypogonadism (IHH) slows the process of metabolic syndrome (MetS), diabetes mellitus, and cardiovascular diseases by its inversing effects on insulin resistance, dyslipidemia, and blood pressure. Since there are not enough data regarding the effects of gonadotropin replacement therapy (GRT), we aimed to investigate the impact of GRT on MetS parameters in IHH patients. Sixteen patients with IHH and 20 age and body mass index (BDI)-matched healthy controls were enrolled into the study. Patients were evaluated at baseline and 6 months after the GRT. Sex hormones, insulin like growth factor-1, prolactin, insulin, C-reactive protein (CRP), homocysteine, and lipid levels were measured at baseline and after the treatment. Anthropometric measurements, including BMI, body fat ratio (BFR), fat free mass (FFM), waist circumference, and waist-to-hip ratio (WHR), were also performed. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) index was calculated. Body fat ratio, triglyceride, HOMA-IR, and CRP levels were higher, whereas bone age, fat free mass, and creatinine levels were lower in the patients with hypogonadism. HOMA-IR indices and basal insulin levels decreased significantly after 6 months of GRT compared with baseline levels. Triglyceride levels, and BFRs diminished significantly by an accompanying decline in WHR. FFM of the patients increased following the GRT. No significant changes were detected in CRP, homocysteine, total and LDL-cholesterol levels. Similar to TRT, hCG treatment decreases HOMA-IR, triglyceride levels, BFR and WHRs, and increases FFM in patients with IHH.

Comparison of primary octreotide-lar and surgical treatment in newly diagnosed patients with acromegaly.

OBJECTIVE: The primary aim of the study was to compare the efficacy of Oct-LAR and surgery in terms of controlling IGF-1 and GH levels and tumour volumes. The second aim was to compare two primary treatment modalities in terms of side effects such as pituitary insufficiency, cholelithiasis, metabolic parameters and the effect on quality of life (QoL). DESIGN: The study was a randomized, prospective study. PATIENTS: The 22 patients were consecutively randomized to Oct-LAR and surgical treatment groups. RESULTS: Baseline serum IGF-1 level, tumour volume and GH levels were comparable in the Oct-LAR and surgery groups. No significant differences were detected between the Oct-LAR and the surgery groups in terms of IGF-1 and GH levels at the 3rd and 6th months, but at 12th month, preglucose GH was found to be lower in the surgical treatment group. IGF-1 control and complete biochemical response rates were found to be 27% and 64%, in the Oct-LAR and surgical treatment groups, respectively. The mean percentage of tumour volume reduction was found to be 26%, 30% and 31% in the Oct-LAR group vs 64%, 74% and 79% in the surgery group at the 3rd, 6th and 12th months, respectively. CONCLUSION: Primary surgical treatment seems to be slightly more effective than Oct-LAR in terms of biochemical response and IGF-1 control, besides tumour volume reduction, in patients with acromegaly with noninvasive tumours. Oct-LAR is associated with more side effects such as cholelithiasis and glucose metabolism disorders and is more expensive.

PILE: a candidate prognostic score in cancer patients treated with immunotherapy.

BACKGROUND: Although the immune checkpoint inhibitors (ICIs) became a vital part of cancer care, many patients do not respond to treatment, indicating need for biomarkers. The Pan-Immune-Inflammation Value (PIV) is a recently developed peripheral blood count-based biomarker. Herein, we evaluated a PIV-based candidate scoring system as a prognostic biomarker in ICI-treated patients. METHODS: A total of 120 advanced cancer patients treated with anti-PD-1 or anti-PD-L1 inhibitors for any cancer type were included in this study. The PILE scoring system incorporating the PIV (< median vs. ≥ median), lactate dehydrogenase levels (normal vs. > normal) and Eastern Cooperative Oncology Group performance status (0 vs. ≥ 1) was constructed from the multivariate analyses and used for stratification. The association between overall survival (OS), progression-free survival and PILE risk category was evaluated with multivariate analysis. RESULTS: The median follow-up was 9.62 months and the median OS of all cohort were 12.42 ± 2.75 months. Patients with higher PIV had significantly decreased OS (7.75 ± 1.64 vs. 18.63 ± 4.26 months, p = 0.037). The patients in the PILE high-risk group (PILE score 2-3) had decreased OS (18.63 ± 4.02 vs. 5.09 ± 1.23 months, HR: 2.317, 95% CI: 1.450-3.700, p < 0.001) and PFS (7.69 ± 1.30 vs. 2.69 ± 0.65 months, HR: 1.931, 95% CI: 1.263-2.954, p = 0.002) compared to PILE low-risk group (PILE score 0-1). The Harrell C-Index values were 0.65 and 0.61 for OS and PFS prediction, respectively. CONCLUSION: In this study, we demonstrated a decreased overall survival in ICI-treated patients with a higher PILE score. If prospective studies validate our results, PILE score could be a biomarker for immunotherapy.

The outcomes of bimanual posterior segment intraocular foreign body removal with vitrectomy and description of two different handshake techniques: A single surgeon case series.

PURPOSE: To evaluate the outcomes of bimanual intraocular foreign body (IOFB) removal with vitrectomy and describe the techniques of "active aspiration to forceps" and "forceps to forceps handshake" for IOFB removal. METHODS: Retrospective, interventional, single surgeon case series. The patients who had an IOFB and underwent vitrectomy with bimanual IOFB removal techniques and had a minimum follow-up period of 12 months were included. The main outcome measure was the functional and anatomical results of the bimanual surgical techniques. RESULTS: Twenty eyes were included. The mean follow-up time after surgery was 16.5±3.6 months (range 12-24 months). The baseline best corrected visual acuity (BCVA) was light perception in 8 eyes (40%), hand motions in one eye (5%), and≥1.0LogMAR in 11 eyes (55%). BCVA improved in 14 eyes (70%); was stable in 3 eyes (15%), and decreased in 3 eyes (15%). CONCLUSIONS: Both bimanual handshake techniques were safe and effective methods in the surgical treatment of IOFBs<5mm in size. The "active aspiration to forceps handshake" technique might be a gentle technique for the removal of IOFBs that are located on the surface of or trapped within the retina.

Comparison of pars plana vitrectomy for retinal detachment after failed pneumatic retinopexy and primary pars plana vitrectomy.

PURPOSE: To compare secondary pars plana vitrectomy (PPV) after failed pneumatic retinopexy (PR) (Group 1) with primary PPV (Group 2) for repair of rhegmatogenous retinal detachment (RRD), with respect to single-procedure reattachment rate and visual outcome. METHODS: A consecutive series of RRD patients treated with PPV following failed PR (n=42) were compared with a selected group of RRD patients who were initially treated with PPV (n=29) with a similar location and distribution of retinal breaks. Main outcomes studied were retinal reattachment rate with single PPV in eyes treated with PPV and gas tamponade or after silicone oil removal in eyes with PPV and SO tamponade, as well as visual acuity at 1-year. RESULTS: The retinal reattachment rate was 90.5% and 93.1% in Group 1 and Group 2, respectively. There was no statistically significant difference in retinal reattachment between groups (P=0.69). Final anatomical reattachment rates after reoperations were 100% in each group. Visual acuity (logarithm of the minimum angle of resolution) improved from 1.95±0.84 at baseline to 0.67±0.35 in Group 1, and from 1.99±1.01 at baseline to 0.65±0.32 in Group 2. Both groups had a significant visual acuity improvement at 1-year compared to baseline (P<0.001 in each of them). Retinal reattachment rate was not associated with lens status (phakic vs pseudophakic) or intraocular tamponade (gas vs silicone oil). Visual outcomes were correlated with macular status at baseline and the number of reoperations. CONCLUSION: This study demonstrates that PPV after failed PR and primary PPV in patients with RRD caused by superiorly located retinal breaks have a similar rate of retinal reattachment along with an improved final VA. Initial success of PPV and macular status may be important predictors of final visual outcomes.

Increased micronucleus, nucleoplasmic bridge, nuclear bud frequency and oxidative DNA damage associated with prolactin levels and pituitary adenoma diameters in patients with prolactinoma.

Prolactinoma is the most common pituitary tumor. Most pituitary tumors are benign, but they often are clinically significant. We investigated cytokinesis-block micronucleus cytome (CBMN cyt) assay parameters and oxidative DNA damage in patients with prolactinoma to assess the relations among age, prolactin level, pituitary adenoma diameter and 8-hydroxy-2'-deoxyguanosine (8-OHdG) level in patients with prolactinoma. We investigated 27 patients diagnosed with prolactinoma and 20 age- and sex-matched healthy controls. We measured CBMN cyt parameters and plasma 8-OHdG levels in peripheral blood lymphocytes of patients with prolactinoma and controls. The frequencies of micronucleus (MN), nucleoplasmic bridge, nuclear bud, apoptotic and necrotic cells, and plasma 8-OHdG levels in patients with prolactinoma were significantly greater than controls. MN frequency was correlated positively with age, prolactin levels and pituitary adenoma diameters in patients with prolactinoma. The increased chromosomal and oxidative DNA damage, and the positive correlation between MN frequency, prolactin levels and pituitary adenoma diameters may be associated with increased risk of cancer in patients with prolactinoma, because increased MN frequency is a predictor of cancer risk.

An alternative approach for enumeration of Escherichia coli in foods.

An assay to screen Escherichia coli in foods using MUG supplemented lauryl sulfate tryptose (LST) broth instead of tryptone water (TW) medium was evaluated. The results presented in this paper suggest that this method is more sensitive for lower levels of E. coli, faster (16-18 h vs. 6-10 days) and less expensive (2.454 vs. 2.887 EURO/sample) than the standard ISO procedure. Thus, this method may be beneficial for use when both fecal coliforms and E. coli analyses are required in food systems.

Mole gun--an unusual firearm, a case note.

There are different kinds of types of firearms used worldwide and of different origin. This case note evaluates the mole gun, which cannot be found in the literature. This simple gun, which is usually used in the fields against moles, was used in an apartment as a trap against burglars. This instrument manufactured to be used as a trap against detrimental animals, and not to be used as a firearm, can create dangerous situations, if used for different purposes.

Shot range estimation based on pellet distribution in shots with a pump-action shotgun.

In the present study, shots from different ranges were fired using a non-choked pump-action shotgun (Hugsan) of calibre 12 with a bore length of 52cm and pellets of various sizes. The aim of the study is range estimation from the distribution of pellets. Using pellets of 2, 3.5, 5 and 8mm size, 5 shots were fired from: 0.7, 0.8, 0.9, 1, 2, 3, 5, 10, 15, 20 and 25ms. The maximum distance between the pellets in vertical and horizontal direction was measured. Statistical evaluation of the data revealed a highly significant correlation for each pellet type; the constant values a and b were calculated to be used in the linear regression equation y=a+bx. As a conclusion, the linear regression equation as well as table data may allow range determination within acceptable ranges of error for the same barrel length and diameter for the same cartridge type. Under identical conditions they may also provide information for pellets of comparable size.

Electrochemical and spectroscopic characteristics of p-acryloyloxybenzoyl chloride and p-acryloyloxybenzoic acid and antimicrobial activity of organic compounds.

The purpose of this multidisciplinary work is to characterize title compounds, p-acryloyloxybenzoyl chloride (ABC) and p-acryloyloxybenzoic acid (ABA) by means of experimental and theoretical evidences. As experimental research, Fourier transformation-infrared spectra (in the region 400-4000 cm(-1)) and nuclear magnetic resonance (NMR) chemical shifts (with a frequency of 400 MHz) are examined for spectroscopic properties belonging to the new synthesized compounds. Moreover, the compounds are investigated for antimicrobial activity against various microorganisms (Gram-positive and Gram-negative) by means of the visual inhibition zone technique on the agar media. The experimental results observed indicate that ABA exhibits more powerful inhibitors of microorganisms due to the presence of the hydroxyl group leading to higher reactive system, one of the most striking features of the paper. As for the theoretical studies, the optimized molecular structures, vibrational frequencies, corresponding vibrational spectra interpreted with the aid of normal coordinate analysis based on scaled density functional force field, atomic charges, thermodynamic properties at different temperature, 1H NMR chemical shifts by way of density functional theory (DFT) with the standard (B3LYP) methods at 6-311G++(d,p) basis set combination for the first time. According to findings, the 1H NMR chemical shifts and vibrational frequencies are obtained to be in good agreement with the suitable experimental results. Thus, it would be more precise to say that the calculation level chosen is powerful approach for understanding in the identification of the molecules investigated. At the same time, we determine the electrochemical characteristics belonging to the samples via the simulation of translation energy (HOMO-LUMO), molecular electrostatic potential (MEP) and electrostatic potential (ESP) investigations. It is observed that the strong intra-molecular charge transfer (ICT) appears between the donor and acceptor in the both compounds (especially ABA) due to the existence of the strong electronic donating groups and effective π-π* conjugated segments with high electronic donor ability for the electrophilic attack (intermolecular interactions).

VEGFR1 expression is related to lymph node metastasis and serum VEGF may be a marker of progression in the follow-up of patients with differentiated thyroid carcinoma.

OBJECTIVE: Vascular endothelial growth factor (VEGF) and VEGF receptor 1 (VEGFR1) are known to be related to thyroid tumorigenesis. The aim of the study was to examine the expressions and serum levels of VEGF, VEGFR1, IGF1, and IGF1 receptor (IGF1R) in patients with differentiated thyroid carcinoma (DTC) compared with patients with nodular goiter (NG). METHODS: We examined 39 patients with DTC who had a clinical history of at least 2 years and compared them with 25 patients who had a pathological diagnosis of NG after thyroidectomy. Serum VEGF, VEGFR1, and IGF1 levels were measured in both patient groups. The expressions of VEGF, VEGFR1, IGF1, and IGF1R were analyzed by the immunohistochemical method in the paraffin blocks of patients' thyroidectomy samples of the patients. RESULTS: The immunostainings scores for VEGF, VEGFR1, IGF1, and IGF1R were found to be higher in patients with DTC than in those with NG. Only VEGFR1 expression was related to lymph node metastasis at the time of surgery. None of the expressions were related to the long-term prognosis of the patients. Serum VEGF was found to be higher in patients with progressive DTC than in patients in clinical remission. CONCLUSION: The expressions of VEGF and VEGFR1 were shown to be correlated with the expression of IGF1 and IGF1R. VEGFR1 expression may be an important index for the presence of lymph node metastasis at the time of thyroidectomy. Increased serum levels of VEGF may reflect disease recurrence in DTC.

PILE: a candidate prognostic score in cancer patients treated with immunotherapy

Background Although the immune checkpoint inhibitors (ICIs) became a vital part of cancer care, many patients do not respond to treatment, indicating need for biomarkers. The Pan-Immune-Inflammation Value (PIV) is a recently developed peripheral blood count-based biomarker. Herein, we evaluated a PIV-based candidate scoring system as a prognostic biomarker in ICI-treated patients. Methods A total of 120 advanced cancer patients treated with anti-PD-1 or anti-PD-L1 inhibitors for any cancer type were included in this study. The PILE scoring system incorporating the PIV (< median vs. ≥ median), lactate dehydrogenase levels (normal vs. > normal) and Eastern Cooperative Oncology Group performance status (0 vs. ≥ 1) was constructed from the multivariate analyses and used for stratification. The association between overall survival (OS), progression-free survival and PILE risk category was evaluated with multivariate analysis. Results The median follow-up was 9.62 months and the median OS of all cohort were 12.42 ± 2.75 months. Patients with higher PIV had significantly decreased OS (7.75 ± 1.64 vs. 18.63 ± 4.26 months, p = 0.037). The patients in the PILE high-risk group (PILE score 2–3) had decreased OS (18.63 ± 4.02 vs. 5.09 ± 1.23 months, HR: 2.317, 95% CI: 1.450–3.700, p < 0.001) and PFS (7.69 ± 1.30 vs. 2.69 ± 0.65 months, HR: 1.931, 95% CI: 1.263–2.954, p = 0.002) compared to PILE low-risk group (PILE score 0–1). The Harrell C-Index values were 0.65 and 0.61 for OS and PFS prediction, respectively. Conclusion In this study, we demonstrated a decreased overall survival in ICI-treated patients with a higher PILE score. If prospective studies validate our results, PILE score could be a biomarker for immunotherapy. (AU)

Molecular differentiation of Lactococcus lactis subspecies lactis and cremoris strains by ribotyping and site specific-PCR.

Twenty-five strains of Lactococcus lactis subspecies lactis and subspecies cremoris obtained from dairy industry and environmental collections were examined by 16S RNA automated ribotyping profiles and site-specific PCR (S-PCR). By automated ribotyping, the majority of strains were classified in accordance with phenotypic characterization, with the exception of one lactis (220) and two cremoris (BO32 and 140) strains. A complete differentiation of subspecies lactis and cremoris in agreement with conventional phenotypic methods was achieved by S-PCR with a set of site-specific primer pairs (PR1, RM4, and F3) designed particularly from a deletion region found in subspecies cremoris, but not in lactis. Therefore, S-PCR with primers (PR1, RM4, and F3) is a rapid and very sensitive method for the distinction of lactis and cremoris subspecies in dairy production.

Comparison of LST + MUG broth technique and conventional method for the enumeration of Escherichia coli in foods.

AIMS: To reduce the analysis time needed for the enumeration of Escherichia coli, a rapid fluorogenic method (MUG) which takes only 48 h was compared with the standard most probable number (MPN) method which takes 6 days as described in the International Standards Organization (ISO). This study provides reliability data for the fluorogenic method applied to certain foods. METHODS AND RESULTS: Both methods were applied to 500 food samples which were analysed for E. coli enumeration. Agreement between the two methods was found in 409 (81 x 8%) samples; 81 (16 x 2%) samples gave higher values by the fluorogenic method, and only 10 (2 x 0%) samples were more effectively assayed by the ISO method. According to statistical analysis, the reliability between the methods was r = 0 x 9706, r(2) = 0 x 9421 and Cronbach's alpha = 0 x 9851. While all three values showed a high degree of correlation (P < 0 x 0001) between the two methods, McNemar's test demonstrated a significant difference between them, indicating that the MUG method was more reliable than the ISO method. CONCLUSIONS: The data suggest that the fluorogenic method is more reliable and shorter to perform than the standard ISO method. SIGNIFICANCE AND IMPACT OF THE STUDY: Comparison of the two methods may provide a rapid and more reliable alternative for the enumeration of E. coli in food samples.