Effect of patient positioning on carbon-ion therapy planned dose distribution to pancreatic tumors and organs at risk

PurposePancreatic tumor treatment dose distribution variations associated with supine and prone patient positioning were evaluated.MethodsA total of 33 patients with pancreatic tumors who underwent CT in the supine and prone positions were analyzed retrospectively. Gross tumor volume (GTV), planning target volume (PTV), and organs at risk (OARs) (duodenum and stomach) were contoured. The prescribed dose of 55.2 Gy (RBE) was planned from four beam angles (0°, 90°, 180°, and 270°). Patient collimator and compensating boli were designed for each field. Dose distributions were calculated for each field in the supine and prone positions. To improve dose distribution, patient positioning was selected from supine or prone for each beam field.ResultsCompared with conventional beam angle and patient positioning, D2cc of 1st-2nd portion of duodenum (D1-D2), 3rd-4th portion of duodenum (D3-D4), and stomach could be reduced to a maximum of 6.4 Gy (RBE), 3.5 Gy (RBE), and 4.5 Gy (RBE) by selection of patient positioning. V10 of D1-D2, D3-D4, and stomach could be reduced to a maximum of 7.2 cc, 11.3 cc, and 11.5 cc, respectively. D95 of GTV and PTV were improved to a maximum of 6.9% and 3.7% of the prescribed dose, respectively.ConclusionsOptimization of patient positioning for each beam angle in treatment planning has the potential to reduce OARs dose maintaining tumor dose in pancreatic treatment.     

Quantification of abdominal and pelvic floor muscle synergies in response to voluntary pelvic floor muscle contractions

The relative levels of pelvic floor muscle (PFM) activation and pressure generated by maximum voluntary PFM contractions were investigated in healthy continent women. The normal sequence of abdominal and PFM activation was determined.Fifteen women performed single and repeated maximum voluntary PFM contractions in supine, sitting and standing. PFM electromyographic (EMG) signals and associated intra-vaginal pressure data were recorded simultaneously. Surface EMG data were recorded from rectus abdominus (RA), external obliques (EO), internal obliques (IO) and transversus abdominus (TA).Abdominal and PFM EMG and intra-vaginal pressure amplitudes generated during voluntary PFM contractions were not different among the positions. Muscle activation sequence differed by position. In supine, EO activation preceded all other muscles by 27 ms (p = 0.043). In sitting, all of the muscles were activated simultaneously. In standing, RA and EO were activated 11 and 17 ms, respectively, prior to the PFMs and TA and IO were activated 10 and 12 ms, respectively, after the PFMs (p ≪ 0.001).The results suggest that women are able to perform equally strong PFM contractions in supine, sitting and standing, however the pattern of abdominal and PFM activation varies by position. These differences may be related to position-dependent urine leakage in women with stress incontinence.     

Lymphocytic Thyroiditis is Associated with Increased Number of Benign Cervical Nodes and Fewer Central Neck Compartment Metastatic Lymph Nodes in Patients with Differentiated Thyroid Cancer

Objective: Whether or not autoimmune thyroid disease influences the progression of differentiated thyroid cancer (DTC) remains controversial. Findings of previous studies are influenced by lead time bias and/or procedure bias selection. These biases can be reduced by studying a single-institution patient population that underwent a similar extent of surgical resection.Methods: From a cohort of 660 patients with DTC who underwent thyroidectomy, we retrospectively studied 357 patients who underwent total thyroidectomy and central compartment node dissection (CCND) for DTC between 2003 and 2013.Results: Forty-one percent (140/345) of study patients had lymphocytic thyroiditis (LT), and 30% (91/301) had serum positive for thyroglobulin antibody (TgAb). LT was reported in 78% of the TgAb-positive cases. Sixty percent (213/357) of cases had metastatic thyroid carcinoma in 1 or more neck lymph nodes (55% [198/357] central compartment, and 22% [77/356] lateral compartment). Patients with LT had fewer metastatic cervical lymph nodes than those with no LT (2.7 ± 4.7 vs 3.5 ± 4.8, respectively, P = .0285). Patients with positive TgAb and thyroiditis had a larger number of benign cervical lymph nodes removed than those with negative TgAb or no LT. No significant difference was observed in age, tumor size, multifocality, extrathyroidal extension, vascular invasion, or frequency of cervical lymph node metastasis between TgAb-negative and -positive cases or between cases with and without LT.Conclusion: Lymphocytic thyroiditis is associated with fewer central neck compartment metastatic lymph nodes and a larger number of excised reactive benign cervical lymph nodes. Whether this association indicates a protective role of thyroid autoimmunity in lymph node spreading remains unclear.Abbreviations:CCND = central compartment node dissectionDTC = differentiated thyroid cancerHT = Hashimoto thyroiditisLT = lymphocytic thyroiditisTgAb = thyroglobulin antibodyTPO = thyroid peroxidase     

Impacto asistencial tras la introducción de la ecografía tiroidea en una unidad monográfica de atención al nódulo tiroideo

IntroductionWorldwide incidence of thyroid cancer has increased in recent decades.ObjectiveTo provide evidence of the diagnostic and care efficiency of a monographic thyroid nodule clinic integrating clinical examination, ultrasound examination, and cytology with on site evaluation.Patients and methodsPatients attending the monographic thyroid nodule clinic from January 2004 to June 2010. Two periods may be distinguished based on availability of ultrasound equipment at the time of the visit: a first period (P1: 01/2004-09/2007) where no ultrasound equipment was available at the clinic and FNA by palpation was performed, and a second period (P2: 10/2007-06/2010) where this equipment was available and ultrasound-guided FNA was performed.ResultsA total of 1036 patients [P1: 537 (52%), P2: 499 (48%)] were seen and enrolled.Diagnostic efficiency (P1 vs P2): 143 vs 181 patients were seen annually, p < 0.001; FNA number/nodule: 1.68 vs 1.17, p < 0.001; percent FNAs with inadequate material: 26% vs 5.3%, p < 0.001; mean (SD) nodule size: 23.6 (12.4) vs 21.7 (11.7) mm, p 0.040; proportion of nodules examined less than 10 mm in size: 9.9% vs 13.7%, p 0.030.Care efficiency: mean time (range) from the first visit to surgery indication: 332 (0-2177) vs 108 (0-596) days, p < 0.001; proportion of patients referred for surgery due to suspect cytology/other reasons: 1.06 vs 2.21, p < 0.001; and operated benign neoplasm/pathology: 0.47 vs 0.93, p = 0.002.ConclusionA monographic thyroid nodule clinic integrating clinical examination, ultrasound, and cytology evaluated on site increases diagnostic and care efficiency in patients with thyroid nodules.     

Sedentary work and the risks of colon and rectal cancer by anatomical sub-site in the Canadian census health and environment cohort (CanCHEC)

BackgroundSedentary behaviour is a potential risk factor for colorectal cancer. We examined the association between sedentary work, based on body position, and colorectal cancer risk in Canadians.MethodsA working body position category (a. sitting; b. standing and walking; c. sitting, standing, and walking; d. other) was assigned to occupations reported by 1991 Canadian Census respondents based on national occupational counselling guidelines. Adjusted hazard ratios (HRs) and 95% confidence intervals (CI) were estimated for cancers of the colon (overall, proximal, and distal) and rectum in men and women newly diagnosed from 1992 to 2010.ResultsCompared to “sitting” jobs, men in occupations with “other” (non-sitting, −standing, or −walking) body positions had a weakly significant reduced colon cancer risk (HR = 0.93, 95% CI: 0.89, 0.98) primarily attributed to protection at the distal site (HR = 0.90, 95% CI: 0.84, 0.97). Men in “standing and walking” and “sitting, standing, and walking” jobs did not have significantly reduced colon cancer risks. No effects were observed for rectal cancer in men or colon and rectal cancer in women.ConclusionThe two significant findings of this analysis should be followed-up in further investigations with additional information on potential confounders. Null findings for rectal cancer were consistent with other studies.     

Assay of Free Thyroxine and Free Triiodothyronine in Fine-Needle Aspiration of Thyroid Nodules: a Useful and Low-Cost Assessment

ObjectiveTo evaluate whether analysis of thyroid hormones in fine-needle aspiration (FNA) of thyroid nodules can provide information about the functional status and the nature of the nodules.MethodsWe studied 4 groups of patients: group 1, 17 patients with autonomous hyperfunctioning thyroid nodules; group 2, 52 patients with cold nonfunctioning thyroid nodules; group 3, 12 patients with malignant thyroid nodules; and group 4 (control group), 10 patients with nonthyroid nodular lesions (enlarged parathyroid glands or lymph nodes). The assay of thyroid hormones was performed in FNA after the washing of needles and, with patient consent, also in normal thyroid parenchyma.ResultsThe free thyroxine (FT₄) and free triiodothyronine (FT₃) values were remarkably high in group 1 (mean, 5.5 ± 0.53 ng/dL and 27.6 ± 3.1 pg/mL, respectively; P < 0.05 versus group 2 and group 4, the control group). The levels of FT₄ and FT₃ were very low in group 3 (< 0.2 ng/dL and < 1.0 pg/mL, respectively; P < 0.05 versus group 2). Thyroglobulin values in FNA specimens were much higher than the normal range in human serum, but no significant differences were found between the various groups. The control group had low levels of FT₄ and FT₃ (< 0.2 ng/dL and < 1.0 pg/mL, respectively) in conjunction with low levels of thyroglobulin, whereas parathyroid hormone levels were high in parathyroid nodules.ConclusionThese results show that assay of FT₄ and FT₃ in FNA can yield information about the functional status of thyroid nodules and, indirectly, about the nature of nodules. In this era of sophisticated new molecular markers in FNA cytology, this low-cost diagnostic method can be readily performed in every laboratory. (Endocr Pract. 2004;10:311-316)     

No Benefit of Dedicated Thyroid Nodule Screening in Patients with Acromegaly

Objective: Acromegaly results from the excessive production of growth hormone and insulin-like growth factor-1. While there is up to a 2-fold increased prevalence of thyroid nodules in patients with acromegaly, the incidence of thyroid cancer in this population varies from 1.6 to 10.6% in several European studies. The goal of our study was to determine the prevalence of thyroid nodules and thyroid cancer among patients with acromegaly at a large urban academic medical center in the United States (U.S.).Methods: A retrospective chart review was performed of all patients with acromegaly between 2006–2015 within the University of California, Los Angeles health system. Data were collected regarding patient demographics, thyroid ultrasounds, thyroid nodule fine needle aspiration (FNA) biopsy cytology, and thyroid surgical pathology.Results: In this cohort (n = 221, 49.3% women, mean age 53.8 ± 15.2 &lsqb;SD] years, 55.2% Caucasian), 102 patients (46.2%) underwent a thyroid ultrasound, from which 71 patients (52.1% women, mean age 52.9 ± 15.2 &lsqb;SD] years, 56.3% Caucasian) were found to have a thyroid nodule. Seventeen patients underwent a thyroid nodule FNA biopsy and the results revealed 12 benign biopsies, 1 follicular neoplasm, 3 suspicious for malignancy, and 1 papillary thyroid cancer (PTC), from which 6 underwent thyroidectomy; PTC was confirmed by surgical pathology for all cases (8.5% of all nodules observed).Conclusion: In this sample, the prevalence of thyroid cancer in patients with acromegaly and coexisting thyroid nodules is similar to that reported in the general U.S. population with thyroid nodules (7 to 15%). These findings suggest that there is no benefit of dedicated thyroid nodule screening in patients newly diagnosed with acromegaly.Abbreviations: AACE = American Association of Clinical Endocrinologists; ATA = American Thyroid Association; DTC = differentiated thyroid cancer; FNA = fine needle aspiration; GH = growth hormone; IGF-1 = insulin-like growth factor-1; PTC = papillary thyroid cancer; U.S. = United States     

Differences between motor point and innervation zone locations in the biceps brachii. An exploratory consideration for the treatment of spasticity with botulinum toxin

BackgroundBotulinum toxin (BTX) acts on the neuromuscular junction which can be located by the innervation zone (IZ). Clinically, the motor point (MP) is homologous to the IZ and it is used as the injection site of BTX. Differences in the effectiveness of the application of BTX between MP and IZ locations have been determined.ObjectiveCompare the location of the MP obtained using electrical stimulation and the location of the IZ using a linear surface electrodes array on the biceps brachii muscle.MethodsThe biceps brachii muscle of twenty men was assessed. The MP was located using the torque measurement generated by electrical stimulation. The IZ was detected using a linear surface electrodes array.ResultsA difference between the MP and the IZ positions (75.8 vs. 86.5 mm, delta 10.7 mm; p = 0.003, post-hoc power 0.89) was observed.DiscussionThe magnitude of the difference between the MP and the IZ may be clinically relevant. The IZ location using surface electromyography as a guide to optimize BTX injection is proposed.     

Exploring the molecular determinants of substrate-selective inhibition of cyclooxygenase-2 by lumiracoxib

Lumiracoxib is a substrate-selective inhibitor of endocannabinoid oxygenation by cyclooxygenase-2 (COX-2). We assayed a series of lumiracoxib derivatives to identify the structural determinants of substrate-selective inhibition. The hydrogen-bonding potential of the substituents at the ortho positions of the aniline ring dictated the potency and substrate selectivity of the inhibitors. The presence of a 5′-methyl group on the phenylacetic acid ring increased the potency of molecules with a single ortho substituent. Des-fluorolumiracoxib (2) was the most potent and selective inhibitor of endocannabinoid oxygenation. The positioning of critical substituents in the binding site was identified from a 2.35 Å crystal structure of lumiracoxib bound to COX-2.     

Design,synthesis and evaluation of 2,4-disubstituted pyrimidines as cholinesterase inhibitors

A group of 2,4-disubstituted pyrimidine derivatives (7a–e, 8a–e and 9a–d) that possess a variety of C-2 aliphatic five- and six-membered heterocycloalkyl ring in conjunction with a C-4 arylalkylamino substituent were designed, synthesized and evaluated as cholinesterase (ChE) inhibitors. The steric and electronic properties at C-2 and C-4 positions of the pyrimidine ring were varied to investigate their effect on ChE inhibitory potency and selectivity. The structure–activity relationship (SAR) studies identified N-benzyl-2-thiomorpholinopyrimidin-4-amine (7c) as the most potent cholinesterase inhibitor (ChEI) with an IC₅₀ = 0.33 μM (acetylcholinesterase, AChE) and 2.30 μM (butyrylcholinesterase, BuChE). The molecular modeling studies indicate that within the AChE active site, the C-2 thiomorpholine substituent was oriented toward the cationic active site region (Trp84 and Phe330) whereas within the BuChE active site, it was oriented toward a hydrophobic region closer to the active site gorge entrance (Ala277). Accordingly, steric and electronic properties at the C-2 position of the pyrimidine ring play a critical role in ChE inhibition.     

Contribution of Gamma Probe–Guided Surgery to Lateral Approach Completion Thyroidectomy

ObjectiveTo evaluate the effectiveness of gamma probe performed with technetium Tc 99m–labeled pertechnetate in patients who underwent completion thyroidectomy after pathologic detection of incidental thyroid cancer following subtotal thyroidectomy.MethodsIn this prospective study, we evaluated findings from patients with multinodular goiter who underwent gamma probe–guided lateral approach completion thyroidectomy after the pathologic detection of incidental thyroid cancer following subtotal thyroidectomy where partial thyroid tissue was left unilaterally or bilaterally. Patients who underwent the procedure between January 2003 and January 2007 were included. Thyroid scintigraphy; thyroid and neck ultrasonography examinations; and concentrations of thyroid hormones, thyrotropin (TSH), thyroglobulin, and thyroglobulin antibodies were evaluated before the second operation. Patients were administered 3 mCi technetium Tc 99m pertechnetate during anaesthetic induction, and we extracted suspicious thyroid tissue and tissue with activity above background activity levels according to gamma probe. Extracted tissues were evaluated pathologically.ResultsCompletion thyroidectomy was performed in 23 patients. Seventy-nine tissue samples were extracted; 49 were thyroid tissue and 30 were nonthyroid tissue. Mean thyroid tissue to background activity ratio (T:B) was 6.4 ± 3.9 (range, 2-14.3), and mean thyroid bed (after excision) to background activity ratio (Tbed:B) was 1.2 ± 0.2 (range, 0.8-1.7) (P = .001). Mean T:B and Tbed:B ratios of the nonthyroid tissue were 1.2 ± 0.3 (range, 0.2-1.7) and 1.1 ± 0.2 (range, 0.4-1.4), respectively (P = .001). The thyroid tissue T:B ratio was significantly higher than that of nonthyroid tissue (P < .001). Gamma probe labeling contributed to extraction of small amounts of thyroid tissue that could not be viewed by scintigraphy in 43% of patients.ConclusionsUsing gamma labeling, thyroid tissue shows significantly more activity than nonthyroid tissue. Gamma probe helps detect small, residual thyroid tissue that is buried in the scar tissue that cannot be distinguished by scintigraphy; therefore, it assists in the extraction of the maximum amount of thyroid tissue. (Endocr Pract. 2009;15:213-219)     

Optimal Free Thyroxine Levels for Thyroid Hormone Replacement in Hypothyroidism

ObjectiveTo determine whether a difference exists in the free thyroxine level required to achieve a normal thyrotropin (thyroid-stimulating hormone or TSH) level between patients with primary hypothyroidism and euthyroid control subjects and compare the free thyroxine levels in patients with primary and secondary hypothyroidism receiving thyroid hormone replacement.MethodsWe retrospectively assessed TSH and free thyroxine values in 58 patients with primary hypothyroidism and 78 euthyroid control subjects for whom screening thyroid function tests had been performed. From the medical records, we also obtained free thyroxine values for 23 patients with central hypothyroidism receiving stable levothyroxine replacement therapy.ResultsThe mean free thyroxine level was significantly higher in patients with primary hypothyroidism than in euthyroid control subjects (1.36 ± 0.201 ng/dL versus 1.10 ± 0.155 ng/dL, respectively, P < .0001), whereas the corresponding mean TSH concentrations did not differ significantly (1.60 ± 1.183 mlU/L versus 1.73 ± 0.792 mlU/L, P = .46). The mean free thyroxine value was also significantly higher in the patients with central hypothyroidism in comparison with that in the euthyroid control subjects (1.31 ± 0.278 ng/dL versus 1.10 ± 0.155 ng/dL, respectively, P < .0001), and no significant difference was noted between the patients with primary and central hypothyroidism (1.36 ng/dL versus 1.31 ng/dL, P = .60).ConclusionPatients with hypothyroidism require a higher level of serum free thyroxine to achieve a normal TSH value in comparison with euthyroid control subjects. This finding suggests that patients with central hypothy-roidism should be treated to achieve free thyroxine levels in the upper part of the reference range. (Endocr Pract. 2008;14:550-555)     

Fine-Needle Aspiration Biopsy of Thyroid Nodules: Comparison of Diagnostic Performance of Experienced and Inexperienced Physicians

ObjectiveTo determine whether a difference exists in terms of obtaining adequate cytologic samples from ultrasound-guided fine-needle aspiration cytology (US-FNAC) between experienced and inexperienced physicians in a tertiary referral center.MethodsIn a prospective design, all patients with thyroid nodules of at least 10 mm in diameter were referred for US-FNAC tissue sampling as a part of their diagnostic work-up. Between May 2006 and September 2009, 997 euthyroid patients with 1, 320 thyroid nodules were referred for US-FNAC by the attending endocrinologist (experienced physician) or 1 of 2 endocrinology fellows (inexperienced physicians).ResultsOf the 1, 320 nodules, 713 biopsy specimens were obtained by the experienced physician and 607 were obtained by the inexperienced physicians. Nodule size was significantly larger in the endocrinologist’s group of patients than in the fellows’ group of patients (17 mm versus 14 mm, respectively; P < .001). The inadequacy rate of the US-FNAC procedures performed by the experienced physician (22 of 713 thyroid nodules or 3.1%) was significantly lower than for those performed by the inexperienced physicians (102 of 607 thyroid nodules or 16.8%) (P < .001).ConclusionWe conclude that, with increasing operator experience, the number of inadequate cytologic specimens generated by US-FNAC procedures is substantially reduced. This limits both direct and indirect costs and also minimizes the risks of possibly unnecessary surgical procedures. (Endocr Pract. 2010;16:986-991)     

Health-Related Quality of Life After Percutaneous Radiofrequency Ablation of Cold,Solid, Benign Thyroid Nodules: A 2-Year Follow-Up Study in 40 Patients

Objective: We studied the impact of radiofrequency ablation (RFA) on health-related quality of life (HRQL) in patients with benign thyroid nodules (TN) in a 2-year follow-up.Methods: Forty patients (35 women and 5 men; age, 54.9 ± 14.3 years) with cold thyroid solitary nodules or a dominant nodule within a normofunctioning multi-nodular goiter (volume range, 6.5 to 90.0 mL) underwent RFA of thyroid nodular tissue under ultrasound real-time assistance.Results: Data are mean and standard deviation. Energy delivered was 37,154 ± 18,092 joules, with an output power of 37.4 ± 8.8 watts. Two years after RFA, nodule volume decreased from 30.0 ± 18.2 mL to 7.9 ± 9.8 mL (-80.1 ± 16.1% of initial volume; P<.0001). Thyroid-stimulating hormone, free triiodothyronine, and free thyroxine levels remained stable. Symptom score measured on a 0- to 10-cm visual analogue scale (VAS) declined from 5.6 ± 3.1 cm to 1.9 ± 1.3 cm (P<.0001). Cosmetic score (VAS 0–10 cm) declined from 5.7 ± 3.2 cm to 1.9 ± 1.5 cm (P<.0001). Two patients became anti-thyroglobulin antibody–positive. Physical Component Summary (PCS)-12 improved from 50.4 ± 8.9 to 54.5 ± 5.3, and the Mental Component Summary (MCS)-12 improved from 36.0 ± 13.3 to 50.3 ± 6.3 (P<.0001 for both score changes).Conclusion: Our 2-year follow-up study confirms that RFA of benign TNs is effective in reducing nodular volume and compressive and cosmetic symptoms, without causing thyroid dysfunction or life-threatening complications. Our data indicate that the achievement of these secondary endpoints is associated with HRQL improvement, measured both as PCS and MCS.Abbreviations: fT₃ = free triiodothyronine fT₄ = free thyroxine HRQL = health-related quality of life MCS-12 = Mental Component Summary-12 PLA = percutaneous laser ablation PCS-12 = Physical Component Summary-12 RF = radiofrequency RFA = radiofrequency ablation SF-12 = Short-Form 12 Health Survey TgAb = anti-thyroglobulin antibody TN = thyroid nodule TRAb = anti-TSH-receptor antibody TSH = thyroid-stimulating hormone US = ultrasound VAS = visual analogue scale     

Effect of Epoprostenol on The Thyroid Gland: Enlargement and Secretion of Thyroid Hormone

ObjectiveTo demonstrate the direct stimulation of thyroid tissue in the absence of thyroid-stimulating immunoglobulin after exposure to epoprostenol.MethodsSeronegative thyrotoxicosis, diffuse goiter, and homogeneous uptake on thyroid scintigraphy were noted in a patient with pulmonary arterial hypertension (PAH) being treated with intravenously administered epoprostenol (prostaglandin I₂ or PGI₂). More cases with similar characteristics were identified on review of the thyroid function in patients with PAH who were treated with this medication. Fifty-four adult patients with PAH were studied. The study subjects were divided into 2 groups based on whether they were treated with PGI₂ or not. Thyroid functions were reviewed, and the prevalence of thyroid disease was assessed. We then compared the prevalence of hyperthyroidism in our study subjects with the prevalence of hyperthyroidism in the general female population using data from published studies.ResultsWe noted a high prevalence (3 of 45 or 6.7%) of thyroid-stimulating immunoglobulin-negative thyrotoxicosis in adults with preexisting PAH being treated with epoprostenol (PGI₂) in the absence of other mechanisms or drugs to explain the hyperthyroidism. The prevalence of hyperthyroidism in our study population was significantly greater (P < .01 by χ² analysis) than that in the general female population in other published reports.ConclusionThe data suggest that epoprostenol is a medication associated with stimulation of thyroid tissue, goiter formation, and hyperthyroidism. Patients receiving this drug need to undergo close follow-up for the development of thyrotoxicosis and goiter. (Endocr Pract. 2009; 15:116-121)     

Quality of Life in Patients with Low-Risk Papillary Thyroid Microcarcinoma: Active Surveillance Versus Immediate Surgery

Objective: This study aimed to compare the quality of life (QoL) and psychological issues of patients with papillary thyroid microcarcinoma (PMC) who were under active surveillance (AS) and those who underwent immediate surgery (OP).Methods: This was a cross-sectional study conducted on 347 patients with low-risk PMC who were under AS (n = 298) or who underwent OP (n = 49). They were asked to complete two questionnaires (thyroid cancer–specific health-related QoL [THYCA-QoL] and the Hospital Anxiety and Depression Scale [HADS]). The results between the AS and OP groups were compared.Results: The mean ages of patients in the AS and OP groups were 58.6 ± 12.5 and 58.4 ± 13.1 years (P =.94), respectively, and the male ratios were 34/298 (11%) and 2/49 (4.1%) (P =.14), respectively. The median follow-up periods from diagnosis in the AS and OP groups were 56.5 months (interquartile range [IQR], 32 to 88 months) and 84 months (IQR, 64 to 130 months) (P<.001), respectively. In the THYCA-QoL questionnaire, the OP group had more complaints about “voice” (P<.001), “psychological” (P =.025), “problems with scar” (P<.001), and “gained weight” (P =.047) than the AS group. Other scales of the THYCA-QoL were comparable in the two groups. In the HADS questionnaire, the AS group had significantly better anxiety (P =.020), depression (P =.027), and total scores (P =.014) than the OP group.Conclusion: PMC patients in the OP group had more complaints and were more anxious and depressed than the AS group. These findings suggest that AS is a reasonable alternative to surgery for patients with low-risk PMC from the point of view of QoL and psychology.Abbreviations: AS = active surveillance; CI = confidence interval; HADS = Hospital Anxiety and Depression Scale; LT4 = levothyroxine; OP = immediate surgery; PMC = papillary microcarcinoma; PTC = papillary thyroid carcinoma; QoL = quality of life; STAI = State-Trait Anxiety Inventory; THYCA-QoL = thyroid cancer–specific health-related quality of life; TSH = thyrotropin     

Higher Serum Osteoprotegerin Levels In Subjects With Thyroid Nodules

Objective: A recent study demonstrated that osteoprotegerin (OPG) could be expressed both in benign and malignant thyroid tissue. However, epidemiologic studies investigating the association between serum OPG and thyroid nodules are not available. The objective of this study was to determine whether serum OPG is associated with thyroid nodules.Methods: We measured serum OPG, total triiodothyronine, total thyroxine, free triiodothyronine, free thyroxine, thyrotropin, antithyroid peroxidase antibodies, thyrotropin-receptor antibodies, antithyroglobulin antibodies, and thyroglobulin in 1,120 Chinese participants in a cross-sectional community-based study performed in downtown Shanghai. Thyroid nodule was diagnosed by thyroid ultrasonographic examination.Results: The serum OPG levels were significantly increased in nodule-positive subjects compared to nodule-negative subjects (2.8 ± 1.2 ng/mL versus 2.1 ± 1.0 ng/mL; P<.001). After multiple adjustments, the odds ratios were substantially higher for thyroid nodule (odds ratio, 3.09; 95% confidence interval, 1.60 to 5.97) in the highest OPG quartile compared with those in the lowest quartile. These associations remained significant after further adjustment for potential confounders. Multivariate linear regression analysis demonstrated that age (P = .015) and OPG (P = .003) were independently associated with thyroid nodule.Conclusion: Serum OPG is elevated significantly in subjects with thyroid nodules among middle-aged and elderly individuals.Abbreviations:BMI = body mass indexCI = confidence intervalDBP = diastolic blood pressureFT3 = free triiodothyronineFT4 = free thyroxineOPG = osteoprotegerinOR = odds ratioRANKL = receptor activator of nuclear factor kappa ligandSBP = systolic blood pressureTg = thyroglobulinTGAb = antithyroglobulin antibodyTPOAb = antithyroid peroxidase antibodyTRAb = thyrotropin-receptor antibodyTRAIL = Tumor necrosis factor–related apoptosis-inducing ligandTSH = thyrotropinTT3 = total triiodothyronineTT4 = total thyroxine     

Synthesis,biological evaluation,and molecular docking studies of novel 1,3,4-oxadiazole derivatives possessing benzotriazole moiety as FAK inhibitors with anticancer activity

1,3,4-Oxadiazole derivatives have drawn continuing interest over the years because of their varied biological activities. In order to search for novel anticancer agents, we designed and synthesized a series of new 1,3,4-oxadiazole derivatives containing benzotriazole moiety as potential focal adhesion kinase (FAK) inhibitors. All the synthesized compounds were firstly reported. Among the compounds, compound 4 shows the most potent inhibitory activity against MCF-7 and HT29 cell lines with IC₅₀ values of 5.68 μg/ml and 10.21 μg/ml, respectively. Besides, all the compounds were assayed for FAK inhibitory activity using the TRAP–PCR–ELISA assay. The results showed compound 4 exhibited the most potent FAK inhibitory activity with IC₅₀ values of 1.2 ± 0.3 μM. Docking simulation by positioning compound 4 into the FAK structure active site was performed to explore the possible binding mode. Apoptosis which was analyzed by flow cytometry, demonstrated that compound 4 induced apoptosis against MCF-7 cells. Therefore, compound 4 may be a potential anticancer agent against MCF-7 cancer cell.     

Structure of a dimeric fungal α-type carbonic anhydrase

The crystal structure of Aspergillus oryzae carbonic anhydrase (AoCA) was determined at 2.7 Å resolution and it revealed a dimer, which only has precedents in the α class in two membrane and cancer-associated enzymes. α carbonic anhydrases are underrepresented in fungi compared to the β class, this being the first structural representative. The overall fold and zinc binding site resemble other well studied carbonic anhydrases. A major difference is that the histidine, thought to be the major proton shuttle residue in most mammalian enzymes, is replaced by a phenylalanine in AoCA. This finding poses intriguing questions as to the biological functions of fungal α carbonic anhydrases, which are promising candidates for biotechnological applications.Structured summaryAoCA binds to AoCA by molecular sieving (View interaction)AoCA binds to AoCA X-ray crystallography (View interaction)     

Design,synthesis and biological evaluation of heterocyclic azoles derivatives containing pyrazine moiety as potential telomerase inhibitors

Three series of novel heterocyclic azoles derivatives containing pyrazine (5a–5k, 8a–8k and 11a–11k) have been designed, synthesized, structurally determined, and their biological activities were evaluated as potential telomerase inhibitors. Among the oxadiazole derivatives, compound 5c showed the most potent biological activity against SW1116 cancer cell line (IC₅₀ = 2.46 μM against SW1116 and IC₅₀ = 3.55 μM for telomerase). Compound 8h performed the best in the thiadiazole derivatives (IC₅₀ = 0.78 μM against HEPG2 and IC₅₀ = 1.24 μM for telomerase), which was comparable to the positive control. While compound 11f showed the most potent biological activity (IC₅₀ = 4.12 μM against SW1116 and IC₅₀ = 15.03 μM for telomerase) among the triazole derivatives. Docking simulation by positioning compounds 5c, 8h and 11f into the telomerase structure active site was performed to explore the possible binding model. The results of apoptosis demonstrated that compound 8h possessed good antitumor activity against HEPG2 cancer cell line. Therefore, compound 8h with potent inhibitory activity in tumor growth inhibition may be a potential antitumor agent against HEPG2 cancer cell. Therefore, the introduction of oxadiazole, thiadiazole and triazole structures reinforced the combination of our compounds and the receptor, resulting in progress of bioactivity.