[Discussion on how to optimize active surveillance for low-risk papillary thyroid microcarcinoma in China].

Active surveillance, as a first-line treatment strategy for low-risk papillary thyroid microcarcinoma, has been recommended by guidelines worldwide. However, active surveillance has not been widely accepted by doctors and patients in China. In view of the huge challenges faced by active surveillance, doctors should improve their understanding of the "low risk" of papillary thyroid micropapillary cancer, identify some intermediate or high-risk cases, be familiar with the criteria and methods of diagnosis for disease progression, and timely turn patients with disease progression into more active treatment strategies. By analyzing the long-term cost-effectiveness of active surveillance, it is clear that medical expense is only one cost form of medical activities, and the health cost (thyroid removal and surgical complications) paid by patients due to"over-diagnosis and over-treatment" is the most important. Moreover, the weakening of the patients' social function caused by surgical procedures is a more hidden and far-reaching cost. The formulation of health economic policies (including medical insurance) should promote the adjustment of diagnosis and treatment behavior to the direction which is conducive to the long-term life and treatment of patients, improving the overall health level of society and reducing the overall cost. At the same time, doctors should stimulate the subjective initiative of patients, help them fully understand the impact of various treatment methods on their psychological and physical status, support patients psychologically, and strengthen their confidence in implementing active surveillance. By strengthening multi-disciplinary treatment team and system support, doctors can achieve risk stratification of papillary thyroid microcarcinoma, accurate judgment of disease progress, timely counseling for psychological problems, and long-term adherence to active surveillance. Improving the treatment level of advanced thyroid cancer is the key point of improve the prognosis. It is important to promote the development of active surveillance for low-risk papillary thyroid microcarcinoma. In the future, it is necessary to carry out multi-center prospective research and accumulate research evidence for promoting the standardization process of active surveillance. Standardized active surveillance will certainly benefit specific papillary thyroid microcarcinoma patients.

[Comparison of clinical effects of endoscopic thyroidectomy using the modified gasless transsubclavian approach and traditional open surgery for cN0 unilateral papillary thyroid carcinoma].

Objective: To compare the clinical effects of endoscopic thyroidectomy using a modified gasless transsubclavian approach and the traditional neck approach for unilateral papillary thyroid carcinoma (cN0). Methods: The clinical data of 135 patients with cN0 papillary thyroid carcinoma who underwent unilateral thyroidectomy in the Department of Thyroid Surgery, the First Hospital of Jilin University from October 2020 to November 2022 were retrospectively analyzed. There were 37 males and 98 females, aging (43.2±8.8) years (range: 21 to 59 years). There were 51 cases using the modified gasless transsubclavian approach (TS group) and 84 cases using the traditional neck approach (TN group). Comparative analyses were performed between the operative results of the 2 groups by t-test, Wilcoxon rank sum test, and χ2 test. Results: All endoscopic operations were successfully completed without conversion to the traditional neck approach. Compared to the TN group, the TS group had a longer operation time (M(IQR)) (73.5 (22.5) minutes vs. 90.0 (30.0) minutes, Z=-5.831, P<0.01), more postoperative drainage (60 (25) ml vs. 95 (45) ml, Z=-6.275, P<0.01), higher hospitalization costs (22 687 (3 488) yuan vs. 26 652 (2 431) yuan, Z=-6.944, P<0.01), and a higher rate of parathyroid autotransplantation (15.5% (13/84) vs. 60.8% (31/51), χ2=29.651, P<0.01). There was no significant difference in the total exposure rate of the central compartment, postoperative hospitalization time, the number of dissected lymph nodes, the number of metastatic lymph nodes, C-reactive protein ratio before and after operation, and preoperative and postoperative parathyroid hormone (all P>0.05). Conclusion: Endoscopic thyroidectomy using the modified gasless transsubclavian approach is safe for cN0 papillary thyroid carcinoma, with longer operating time, more postoperative drainage, higher hospitalization costs, and more difficulty in preserving the inferior parathyroid gland in situ compared to traditional open surgery.

[LncRNA ASB16-AS1 regulates the proliferation, migration and invasion of esophageal cancer cells by targeting miR-1258].

Objective: To investigate the effects of long-chain non-coding RNA ASB16 antisense RNA1 (ASB16-AS1) on the proliferation, migration and invasion of esophageal cancer cells by targeting microRNA (miR )-1258. Methods: Forty pairs of esophageal cancer tissues and matched adjacent tissues (distance of tumor margin>3 cm) resected in Xinxiang Central Hospital from May 2016 to July 2017 were collected. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expressions of ASB16-AS1 and miR-1258 in esophageal cancer tissues and adjacent tissues. The small interfering RNA negative control (si-NC), ASB16-AS1 small interfering RNA (si-ASB16-AS1), miR-negative control mimics (miR-NC), miR-1258 mimics (miR-1258), si-ASB16-AS1 and anti-miR-NC, si-ASB16-AS1 and anti-miR-1258, si-ASB16-AS1 and anti-miR-1258 were transfected into Eca109 cells, respectively. Methyl thiazolyl tetrazolium (MTT) was utilized to detect the cell viability. Transwell assays were applied to detect cell migration and invasion. Double luciferase reporting experiment and qRT-PCR were used to confirm the relationship between ASB16-AS1 and miR-1258. Results: The expression levels of ASB16-AS1 and miR-1258 in esophageal cancer tissues were 2.95±0.27 and 0.62±0.06, respectively. Compared with 1.00±0.06 and 1.00±0.07 in adjacent tissues, the difference was statistically significant (P<0.05). The cell viability of the si-NC group at 48 h and 72 h were 0.81±0.07 and 1.15±0.11, while those of si-ASB16-AS1 group were 0.46±0.04 and 0.62±0.06 (P<0.05). The numbers of cell migration and invasion in the si-NC group were 86.32±8.24 and 71.29±7.15, respectively, while those of si-ASB16-AS1 group were 43.22±4.31 and 32.36±3.58, respectively, the differences were statistically significant (P<0.05). The cell viability of the miR-NC group at 48 h and 72 h were 0.84±0.08, 1.18±0.12, while those of miR-1258 group were 0.55±0.05, 0.71±0.07 (P<0.05). The migration and invasion numbers of the miR-NC group were (83.15±8.31) and (75.33±7.51), while those of miR-1258 group were (49.58±4.23) and (38.42±3.84), respectively, the differences were statistically significant (P<0.05). The cell viability of the si-ASB16-AS1+ anti-miR-NC group at 48 h and 72 h were 0.45±0.04, 0.61±0.06, while those of si-ASB16-AS1+ anti-miR-1258 group were 0.72±0.07, 0.98±0.08; The migration and invasion numbers of cells in the si-ASB16-AS1+ anti-miR-NC group were 44.36±4.41 and 31.69±3.85, respectively, while those of si-ASB16-AS1+ anti-miR-1258 group were 72.65±7.27 and 61.22±6.14, respectively, and the differences were statistically significant (P<0.05). ASB16-AS1 targeted negative regulation of miR-1258 expression. Conclusions: ASB16-AS1 upregulates in esophageal cancer. ASB16-AS1 promotes the proliferation, migration and invasion of esophageal cancer cells by targeting miR-1258.

Realizing Magnetoelectric Coupling with Hydrogen Intercalation.

Materials with a coexistence of magnetic and ferroelectric order (i.e., multiferroics) provide an efficient route for the control of magnetism by electric fields. Unfortunately, a long-sought room temperature multiferroic with strongly coupled ferroelectric and ferromagnetic (or ferrimagnetic) orderings is still lacking. Here, we propose that hydrogen intercalation in antiferromagnetic transition-metal oxides is a promising way to realize multiferroics with strong magnetoelectric coupling. Taking brownmillerite SrCoO_{2.5} as an example, we show that hydrogen intercalated SrCoO_{2.5} displays strong ferrimagnetism and large electric polarization in which the hydroxide acts as a new knob to simultaneously control the magnetization and polarization at room temperature. We expect that ion intercalation will become a general way to design magnetoelectric and spintronic functional materials.

Pressure Induced Stripe-Order Antiferromagnetism and First-Order Phase Transition in FeSe.

To elucidate the magnetic structure and the origin of the nematicity in FeSe, we perform a high-pressure ^{77}Se NMR study on FeSe single crystals. We find a suppression of the structural transition temperature with pressure up to about 2 GPa from the anisotropy of the Knight shift. Above 2 GPa, a stripe-order antiferromagnetism that breaks the spatial fourfold rotational symmetry is determined by the NMR spectra under different field orientations and with temperatures down to 50 mK. The magnetic phase transition is revealed to be first-order type, implying the existence of a concomitant structural transition via a spin-lattice coupling. Stripe-type spin fluctuations are observed at high temperatures, and remain strong with pressure. These results provide clear evidence for strong coupling between nematicity and magnetism in FeSe, and therefore support a universal scenario of magnetic driven nematicity in iron-based superconductors.

Clinical analysis of 137 cases of ultrasound-guided positioning for resection of non-palpable breast masses.

OBJECTIVE: The aim of this study was to evaluate the clinical value of ultrasound-guided resection of non-palpable breast masses. MATERIALS AND METHODS: One hundred thirty-seven cases of non palpable breast mass patients who underwent surgical treatment from June 2007 to June 2012 were enrolled in this study. All patients were found with breast masses in mammography or ultrasound, and underwent preoperative routine ultrasound-guided wire positioning. RESULTS: One hundred fifty-eight lesions underwent ultrasound positioning accurate resection, of which 34 cases (21.5%) were malignant, including 26 cases (16.5%) of intraductal carcinoma, four cases (2.5%) of infiltrating ductal carcinoma, and three cases (1.9%) of invasive lobular carcinoma. Thirteen patients underwent modified radical mastectomy, and 21 cases (61.8%) underwent breast conservation operation. All patients were followed up for six to 53 months, only one patient had pulmonary metastasis after two years, and there was no local recurrence. CONCLUSION: Resection of non-palpable breast masses with preoperative ultrasound-guided positioning has advantages of accurate positioning and simple operation and is of great significance for early diagnosis and treatment of breast cancer.

Predicting a ferrimagnetic phase of Zn(2)FeOsO(6) with strong magnetoelectric coupling.

Multiferroic materials, in which ferroelectric and magnetic ordering coexist, are of practical interest for the development of novel memory devices that allow for electrical writing and nondestructive magnetic readout operation. The great challenge is to create room temperature multiferroic materials with strongly coupled ferroelectric and ferromagnetic (or ferrimagnetic) orderings. BiFeO_{3} is the most heavily investigated single-phase multiferroic to date due to the coexistence of its magnetic order and ferroelectric order at room temperature. However, there is no net magnetic moment in the cycloidal (antiferromagneticlike) magnetic state of bulk BiFeO_{3}, which severely limits its realistic applications in electric field controlled memory devices. Here, we predict that LiNbO_{3}-type Zn_{2}FeOsO_{6} is a new multiferroic with properties superior to BiFeO_{3}. First, there are strong ferroelectricity and strong ferrimagnetism at room temperature in Zn_{2}FeOsO_{6}. Second, the easy plane of the spontaneous magnetization can be switched by an external electric field, evidencing the strong magnetoelectric coupling existing in this system. Our results suggest that ferrimagnetic 3d-5d LiNbO_{3}-type material may therefore be used to achieve voltage control of magnetism in future memory devices.

First Report of Cherry Stem Rot and Leaf Necrosis Disease Caused by Phytophthora nicotianae in Yantai, China.

Cherry (Cerasus avium (Linn.) Moench) is the third most economically important fruit in Yantai, Shandong Province, China. In August 2012, brown spots or necrosis on cherry seedling leaves, with an incidence of 8.2 to 34.3%, were observed in some fields of cherry seedlings in Yantai. Our survey indicated that the economic losses could reach up to 15.3% if disease conditions, such as a cool rainy summer season, were favorable. Conspicuous watery lesions on the stems turned to brown streaks; the leaves all wilted; and finally the plants collapsed. Diseased stem and leaf samples were surface-disinfected in 1% sodium hypochlorite for 1 min, rinsed three times in sterile water, which was absorbed with filter paper, and then transferred to 10% V8 juice agar medium containing 50 µg/ml ampicillin and 5 µg/ml carbendazim (1). The plates were incubated at 22°C in the dark for 5 days. The colonies consisted of white, loose, fluffy aerial mycelia. Eight isolates were obtained, and all were identified as Phytophthora nicotianae based on morphological characteristics and the sequence of the internal transcribed spacer (ITS) region of rDNA. The sporangia were ovoid/spherical, obturbinate with rounded bases and prominent papillae that were 37.5 to 62.5 × 30 to 50 µm (average 46.4 × 37.8 µm, n = 100) in size, with an average length-to-breadth ratio of 1.2. Chlamydospores were terminal, intercalary, and measured 19 to 42 µm (average 30.4 µm), which is typical of P. nicotianae (2). The genomic DNA of the eight isolates was extracted from mycelia. The ITS region of all eight isolates was amplified using primers ITS1 and ITS4, producing specific products that were directly sequenced. The sequence of a representative isolate P1401 (895 bp) was submitted to GenBank (Accession No. KJ754387). It was 100% similar to P. nicotianae strains NV-20T and TARI 22073 (KC768775 and GU111667). To confirm the pathogenicity, at least 10 cherry leaves and new stems were inoculated with mycelial plugs (5 × 5 mm) from each isolate. Necrosis of leaves and stems was observed 4 and 7 days after inoculation, respectively. No symptoms were observed on the control leaves and stems that were inoculated with blank agar plugs. P. nicotianae was re-isolated from the infected leaves, and the ITS sequence was analyzed to confirm its identity. Phytophthora species, such as P. cambivora, P. megasperma, and P. drechsleri, had been previously isolated from cherry (3), but to the best of our knowledge this is the first report of stem rot and leaf necrosis disease caused by P. nicotianae on cherry. Since the economic loss caused by this disease could reach 15% if an outbreak occurred in a rainy summer, control measures should be implemented. References: (1) Y. Balci et al. Mycol. Res. 112:906, 2008. (2) D. C. Erwin and O. K. Ribeiro. Phytophthora Diseases Worldwide. The American Phytopathological Society, St Paul, MN, 1996. (2) S. M. Mircetich and M. E. Matheron. Phytopathology 66:549, 1976.

Simultaneous optimization of spin fluctuations and superconductivity under pressure in an iron-based superconductor.

We present a high-pressure NMR study of the overdoped iron pnictide superconductor NaFe0.94Co0.06As. The low-energy antiferromagnetic spin fluctuations in the normal state, manifest as the Curie-Weiss upturn in the spin-lattice relaxation rate 1/(75)T1T, first increase strongly with pressure but fall again at P>Popt=2.2 GPa. Neither long-ranged magnetic order nor a structural phase transition is encountered up to 2.5 GPa. The superconducting transition temperature Tc shows a pressure dependence identical to the spin fluctuations. Our observations demonstrate that magnetic correlations and superconductivity are optimized simultaneously as a function of the electronic structure, thereby supporting very strongly a magnetic origin of superconductivity.

Barriers to mental health treatment: results from the National Comorbidity Survey Replication.

BACKGROUND: The aim was to examine barriers to initiation and continuation of treatment among individuals with common mental disorders in the US general population. METHOD: Respondents in the National Comorbidity Survey Replication with common 12-month DSM-IV mood, anxiety, substance, impulse control and childhood disorders were asked about perceived need for treatment, structural barriers and attitudinal/evaluative barriers to initiation and continuation of treatment. RESULTS: Low perceived need was reported by 44.8% of respondents with a disorder who did not seek treatment. Desire to handle the problem on one's own was the most common reason among respondents with perceived need both for not seeking treatment (72.6%) and for dropping out of treatment (42.2%). Attitudinal/evaluative factors were much more important than structural barriers both to initiating (97.4% v. 22.2%) and to continuing (81.9% v. 31.8%) of treatment. Reasons for not seeking treatment varied with illness severity. Low perceived need was a more common reason for not seeking treatment among individuals with mild (57.0%) than moderate (39.3%) or severe (25.9%) disorders, whereas structural and attitudinal/evaluative barriers were more common among respondents with more severe conditions. CONCLUSIONS: Low perceived need and attitudinal/evaluative barriers are the major barriers to treatment seeking and staying in treatment among individuals with common mental disorders. Efforts to increase treatment seeking and reduce treatment drop-out need to take these barriers into consideration as well as to recognize that barriers differ as a function of sociodemographic and clinical characteristics.

Role of serum- and glucocorticoid-inducible kinase-1 in regulating torsion-induced apoptosis in rats.

Serum- and glucocorticoid-inducible kinase-1 (SGK1) is a serine/threonine protein kinase that responds to various stimuli and mediates cell survival. Although it is known that testicular torsion leads to testicular damage and male infertility, the role of SGK1 in torsion remains unclear. This study investigated whether torsion-induced apoptosis is associated with changes in phosphoinositide-dependent protein kinase-1 (PDK1), SGK1 and forkhead transcription factor FOXO3a expression and/or phosphorylation in rats. Sprague-Dawley rats were divided into four groups: sham (control), 1, 2 and 4 h of unilateral torsion. Bilateral testes, testicular interstitial fluid (TIF) and blood samples were collected immediately after torsion. Our results revealed that SGK1 protein and mRNA were abundantly present in testes and were induced by 2 h of torsion, but that phosphorylation of SGK1, PDK1 and FOXO3a decreased simultaneously. After 2 h of torsion, the testosterone secretion capacity of the primary Leydig cells and testicular interstitial cells (TICs) was impaired and apoptotic spermatogonia and TICs were observed; in addition, the mean seminiferous tubular diameter was decreased. Torsion increased plasma corticosterone levels, but decreased plasma luteinizing hormone and testosterone levels. However, the testosterone levels of the TIF in the ipsilateral testes were significantly enhanced after 2 h of torsion, but suppressed in the contralateral testes. This animal study suggests that PDK1, SGK1 and FOXO3a are involved in torsion-induced apoptosis and that medical therapy should be performed as early as 2 h after the occurrence of torsion to prevent further damage.

Impairment in role functioning in mental and chronic medical disorders in the United States: results from the National Comorbidity Survey Replication.

This study presents national data on the comparative role impairments of common mental and chronic medical disorders in the general population. These data come from the National Comorbidity Survey Replication, a nationally representative household survey. Disorder-specific role impairment was assessed with the Sheehan Disability Scales, a multidimensional instrument that asked respondents to attribute impairment to particular conditions. Overall impairment was significantly higher for mental than chronic medical disorders in 74% of pair-wise comparisons between the two groups of conditions, and severe impairment was reported by a significantly higher portion of persons with mental disorders (42.0%) than chronic medical disorders (24.4%). However, treatment was provided for a significantly lower proportion of mental (21.4%) than chronic medical (58.2%) disorders. Although mental disorders were associated with comparable or higher impairment than chronic medical conditions in all domains of function, they showed different patterns of deficits; whereas chronic medical disorders were most likely to be associated with impairment in domains of work and home functioning, mental disorders were most commonly associated with problems in social and close-relation domains. Comorbidity between chronic medical and mental disorders significantly increased the reported impairment associated with each type of disorder. The results indicate a serious mismatch between a high degree of impairment and a low rate of treatment for mental disorders in the United States. Efforts to reduce disability will need to address the disproportionate burden and distinct patterns of deficits of mental disorders and the potentially synergistic impact of comorbid mental and chronic medical disorders.

The 'hot cross bun' sign in the patients with spinocerebellar ataxia.

BACKGROUND AND PURPOSE: The 'hot cross bun' sign (HCBS), typically seen in the patients with multiple system atrophy, refers to a cruciform hyperintensity in the pons on T2-weighted MRI. Little is known about its pathological basis and prevalence in other degenerative cerebellar diseases and healthy population. We investigate the frequency of HCBS in the patients with spinocerebellar ataxia (SCA) and healthy controls. METHODS: The presence of HCBS on T2-weighted axial MRIs from 138 SCA patients (three SCA1, 35 SCA2, 76 SCA3, 18 SCA6, one SCA7, three SCA8, and two SCA17) and 102 healthy controls was evaluated retrospectively. RESULTS: The overall prevalence of HCBS in the SCA patients is 8.7%, but the frequency varies in different subtypes: 25.7% in SCA2, 1.3% in SCA3, and none in SCA6 or healthy controls. Notably, one patient with SCA7 and one with SCA8 were also found to have HCBS. CONCLUSIONS: The differential list of HCBS should be expanded to include SCA7 and SCA8. The elucidation of frequency of HCBS in various SCA subtypes may help prioritize the genetic testing in late-onset dominant ataxia.

Downregulation of progesterone biosynthesis in rat granulosa cells by adlay (Coix lachryma-jobi L. var. ma-yuen Stapf.) bran extracts.

Adlay (Coix lachryma-jobi L. var. ma-yuen Stapf.) has long been used as a traditional Chinese medicine for dysfunctions of the endocrine system and inflammation conditions. However, the effect of adlay seed on the endocrine system has not yet been reported. In the present study, the effects and the mechanisms of methanolic extract of adlay bran (ABM) on progesterone synthesis in rat granulosa cell were studied. ABM was further partitioned with different solvents including water, 1-butanol, ethyl acetate and n-hexane. Four subfractions named ABM-Wa (water fraction), ABM-Bu (1-butanol fraction), ABM-EA (ethyl acetate fraction) and ABM-Hex (n-hexane fraction) were obtained. ABM-Bu was further fractionated using Diaion HP-20 resin column chromatography with gradient elution. Granulosa cells were prepared from pregnant mare serum gonadotropin-primed immature female rats and challenged with different reagents including human chorionic gonadotropin (hCG 0.5 IU/ml), forskolin (10 microM), 8-bromo-adenosine-3',5'-cyclic monophosphate (8-Br-cAMP, 1 mM), A23187 (10 microM), phorbol 12-myristate 13-acetate (PMA, 0.01 microM), 25-OH-cholesterol (0.1-10 microM) and pregnenolone (0.1-10 microM) in the presence or absence of ABM-Bu (100 microg/ml). The functions of steroidogenic enzyme including protein expression of the steroidogenic acute regulatory protein (StAR) and cytochrome P450 side-chain cleavage enzyme (P450scc) protein were investigated. Expressions of both P450scc and StAR mRNA have also been explored. We found that ABM decreased progesterone production via an inhibition on (1) the cAMP-PKA and PKC signal transduction pathway, (2) P450scc and 3beta-hydroxysteroid dehydrogenase (3beta-HSD) enzyme activity, (3) P450scc and StAR protein and mRNA expressions and (4) the phosphorylation of ERK1/2 in rat granulosa cells.

Antibody to epiglycanin and radioimmunoassay to detect epiglycanin-related glycoproteins in body fluids of cancer patients.

By means of a radioimmunoassay, which utilized [125I]-epiglycanin and anti-epiglycanin antiserum induced in rabbits by injections of viable TA3-Ha ascites cells with Freund's complete adjuvant, picogram quantities of epiglycanin could be detected. Anti-epiglycanin antiserum was similarly produced in allogeneic mice. Unlabeled epiglycanin lost the capacity to compete with [125I]epiglycanin in the radioimmunoassay as a result of periodate oxidation or incubation with endo-alpha-N-acetyl-D-galactosaminidase (Diplococcus pneumoniae), an enzyme found to cleave only the disaccharide beta-D-galactopyranosyl-(1----3)-2-acetamido-2-deoxy-D-galactose chain from serine or threonine residues in epiglycanin. Glycosylhydrolases known to cleave alpha-D-mannose, beta-D-galactose (1,4-linked), beta-N-acetyl-D-glucosamine, and alpha-N-acetyl-D-galactosamine did not reduce the activity of epiglycanin. Neuraminidase enhanced the activity twofold to fivefold. The finding that little or no activity was demonstrated by the disaccharide, the reduced disaccharide, or other glycoproteins containing the same disaccharide chain suggested that the antigenic determinant probably involved the disaccharide and a unique amino acid sequence at the site of its attachment. By means of the radioimmunoassay epiglycanin cross-reactive antigens were detected in the peritoneal or pleural fluid and in the sera of patients with metastatic cancer. Lower concentrations of epiglycanin-like antigen(s) were found in the peritoneal fluid of patients with hepatitis or liver cirrhosis but not in normal serum.

Calcitonin inhibits testosterone and luteinizing hormone secretion through a mechanism involving an increase in cAMP production in rats.

Effects of calcitonin peptides, including human calcitonin (hCT), salmon calcitonin (sCT), and calcitonin gene-related peptide (CGRP), on the secretion of testosterone and luteinizing hormone (LH) in male rats were studied. Male rats were injected intravenously with human chorionic gonadotropin (hCG), calcitonin peptides, or hCG plus calcitonin peptides. Blood samples were collected at several intervals following hormone challenge. In an in vitro experiment, testis blocks were incubated with hCG (0, 0.05, 0.5, or 5 IU/ml) or hCG (0.5 IU/ml) plus calcitonin peptides (0-10(-9) or 10(-6) M) at 34 degrees C for 30 minutes. Both medium and plasma samples were extracted by ether and analyzed for testosterone by radioimmunoassay (RIA). The concentration of calcium in each plasma sample was measured by an automatic calcium analyzer. The anterior pituitary gland (AP) was incubated with or without calcitonin peptides (0-10 nM) at 37 degrees C for 30 minutes. They were then incubated with gonadotropin releasing hormone (GnRH, 10 nM) for a further 30 minutes. The concentration of LH in AP medium was measured by RIA. The accumulation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in both testicular tissues and APs were measured by RIA. A single intravenous injection of calcitonin peptides decreased the basal and hCG-stimulated levels of plasma testosterone gradually from 60 to 180 or 360 minutes after challenge. The plasma calcium was not altered by the injection of calcitonin peptides and/or hCG. Administration of calcitonin peptides in vitro resulted in a dose-dependent inhibition of both basal and hCG-stimulated release of testosterone.(ABSTRACT TRUNCATED AT 250 WORDS)

Unimpaired postreceptor regulation of luteinizing hormone secretion by gonadotropin-releasing hormone and estrogen in aged rat anterior pituitary cells.

Delayed, attenuated, or absence of the proestrous LH surge occurs in aging rats. To assess how aging affects the positive feedback action of 17 beta-estradiol (E2) on the pituitary, we determined the responsiveness of rat pituitary cells to GnRH and the secretagogues affecting intracellular signal transduction mechanisms in the presence or absence of E2. We also correlated the LH response to pituitary LH content. Anterior pituitaries excised from ovariectomized Sprague-Dawley rats, either young (3-4 months) or old (19-20 months), were enzymatically dispersed and then pretreated with or without E2 (0.6 nM) for 48 h, followed by incubation for 3 h with or without various secretagogues. The secretagogues included GnRH (1 and 10 nM), veratridine (increases Ca2+ influx; 5 and 10 microM), and phorbol 12-myristate 13-acetate (a protein kinase-C activator; 10 and 100 nM). LH in media and cells were measured by RIA and expressed on the basis of cellular DNA. GnRH, veratridine, and phorbol 12-myristate 13-acetate at all doses stimulated (P < 0.01) LH release in cells from both young and old rats. E2 stimulated (P < 0.05 to P < 0.01) all secretagogue-induced LH release in cells from both young and old rats, but only basal LH release (P < 0.05) in cells from young rats. The magnitude of both basal and secretagogue-induced LH release in either the presence or absence of E2 was smaller (P < 0.01) in cells from old than in those from young rats. The initial cellular LH was lower (P < 0.01) in cells from old than in those from young rats. The LH-releasing ability (expressed as a percentage of total cellular LH) of cells from old rats was identical (P > 0.05) to that of cells from young rats under all conditions studied. These results suggest that the reduced magnitude of LH release by cells from old rats may be attributed to reduced cellular LH, rather than to impaired estrogen feedback or impaired signal transduction mechanisms. It remains to be determined whether LH biosynthesis per cell and/or the number of gonadotropes decrease with age.

Hazardous benzodiazepine regimens in the elderly: effects of half-life, dosage, and duration on risk of hip fracture.

OBJECTIVE: While benzodiazepine treatment is known to increase the risk of hip fracture in older populations, controversy persists over which characteristics of benzodiazepine use (e.g., elimination half-life, dosage, duration of use) are most associated with such risks. METHOD: The authors reviewed the health care utilization data of 1,222 hip fracture patients and 4,888 comparison patients frequency matched on the basis of age and gender (all were at least 65 years old). Patients were enrolled in Medicare as well as in the New Jersey Medicaid or Pharmaceutical Assistance to the Aged and Disabled programs. Benzodiazepine use, as well as other covariates, were assessed before the index date (which was either the date of hospital admission for hip fracture surgical repair or, for the comparison subjects, a randomly assigned, frequency-matched date). RESULTS: All benzodiazepine doses > or =3 mg/day in diazepam equivalents significantly increased the adjusted risk of hip fracture by 50%. Significantly increased adjusted risks of hip fracture were seen during the initial 2 weeks of use (60% increase) and after more than 1 month of continuous use (80% increase) but not for 2-4 weeks of continuous use. Use of benzodiazepines other than long-acting agents significantly increased the risk of hip fracture by 50%. CONCLUSIONS: Even at modest doses, including some low doses currently advocated in prescribing guidelines for older patients, treatment with benzodiazepines appears to increase the risk of hip fracture. Patients appear to be particularly vulnerable immediately after initiating therapy and after more than 1 month of continuous use. Benzodiazepines with shorter half-lives appear to be no safer than longer half-life agents. Clinicians should be aware of these risks and weigh them against potential benefits when prescribing for elderly patients.

Subarachnoid hemorrhage and family history. A population-based case-control study.

OBJECTIVE: To evaluate family history as a risk factor for subarachnoid hemorrhage. DESIGN AND SETTING: A population-based case-control study in King County, Washington. SUBJECTS: Cases consisted of 149 patients with spontaneous subarachnoid hemorrhage. Two control subjects who were matched to cases by gender and age within 5 years were identified for each case using random digit telephone dialing. MAIN MEASURE: Detailed information on family history was obtained through an in-person interview. RESULTS: Some 11.4% of cases had a first-degree relative with a history of subarachnoid hemorrhage, compared with 6.4% of controls, yielding an odds ratio of 1.8 (95% CI, 0.92 to 3.7). The odds ratio for a positive family history among other relatives was 2.4 (95% CI, 1.1 to 5.2), likely reflecting family information bias. Findings were similar after adjustment was made for potential confounding variables, including cigarette smoking, a history of hypertension, and number of siblings and children. CONCLUSION: Although familial factors may be important in some families, overall they account for few cases of subarachnoid hemorrhage.

Effects of aging on erythropoietin secretion in female rats.

The secretion of erythropoietin (EPO) in old (22 25 months), middle (mid)-aged (15-17 months), adult (6-7 months), and young (3 months) female rats was studied. Rats of different ages were bled by cardiac puncture for measuring plasma EPO, estradiol, and progesterone levels. The metabolic clearance rate of EPO was determined by a single-injection method. The effects of ovariectomy and replacement of estradiol (E) and/or progesterone (P) on plasma EPO concentration were also investigated. Analysis of direct effects of E and/or P on EPO from kidney tissues was carried out in an in vitro study. Plasma EPO levels were higher in both mid-aged and old rats than in young rats (P < 0.01). The metabolic clearance rate of EPO was also greater in adult, mid-aged and old rats than in young rats (P < 0.01). Ovariectomy increased rat plasma EPO concentration which might be inhibited by E (P < 0.01), P (P < 0.01), or E and P (P < 0.05) replacement. Neither E (10(-10) or 10(-9) M) nor P (10(-8) or 10(-7) M) alone altered EPO release from kidney tissue in vitro. Combination of E (10(-10) M) and P (10(-8) x or 10(-7) M) stimulated the EPO release from kidney tissue (P < 0.01). These data suggest that the mechanism of the secretion of EPO by kidneys in female rats during aging is ovarian steroid hormones independent.