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Background: Various methods are used in forensic odontology for the purpose of sex and personal identification. Some of them include cheiloscopy, rugoscopy, mandibular measurements, and study of paranasal sinuses. In our study, we have used maxillary sinus as an aid in sex identification. For this purpose, we have evaluated the morphometric and volumetric measurements of the maxillary sinus using a 3-Dimensional imaging modality, Cone Beam Computed Tomography. Aims and Objectives: Sex and age identification are important in the process of identification of both the living and the dead. Hence, this transverse retrospective study was done to appraise the precision of the dimensions and volume of the maxillary sinus to aid in sex and age identification. Material and Methods: Eighty full Field of View (FOV) Cone-Beam Computed Tomography (CBCT) images were retrieved from the archives which were matched with age and sex. The maxillary sinuses on either side were measured mediolaterally in the axial section and supero-inferiorly in the coronal section. The volumetric analysis of the sinus was done in the sagittal section. The sex was classified using discriminant function analysis and the differences were compared using independent t-test. The differences with age were analyzed using one-way ANOVA. Results: Independent t-test was done for comparison of the sinuses between both sexes. Maxillary sinuses measurements were larger among the males both superior-inferiorly on either side (P

Uridine diphosphate glycosyltransferases (UDP-GTs, UGTs), which are regulated by UGT genes, play a crucial role in glycosylation. In vivo, the activity of UGT genes can affect the availability of metabolites and the rate at which they can be eliminated from the body. UGT genes can exert their regulatory effects through mechanisms such as post-transcriptional modification, substrate subtype specificity, and drug interactions. Phoebe bournei is an economically significant tree species that is endemic to southern China. Despite extensive studies on the UGT gene family in various species, a comprehensive investigation of the UGT family in P. bournei has not been reported. Therefore, we conducted a systematic analysis to identify 156 UGT genes within the entire P. bournei genome, all of which contained the PSPG box. The PbUGT family consists of 14 subfamilies, consistent with Arabidopsis thaliana. We observed varying expression levels of PbUGT genes across different tissues in P. bournei, with the following average expression hierarchy: leaf > stem xylem > stem bark > root xylem > root bark. Covariance analysis revealed stronger covariance between P. bournei and closely related species. In addition, we stressed the seedlings with 10% NaCl and 10% PEG-6000. The PbUGT genes exhibited differential expression under drought and salt stresses, with specific expression patterns observed under each stress condition. Our findings shed light on the transcriptional response of PbUGT factors to drought and salt stresses, thereby establishing a foundation for future investigations into the role of PbUGT transcription factors.

Background The temporomandibular joint (TMJ) is included in the category of ginglymoarthrodial synovial joints. The mandibular condyle plays a vital part in the development of the craniofacial complex. Hence, the evaluation and assessment of the condylar volume and its morphology are of utmost importance. Aim The aim of this research was to use cone beam computed tomography (CBCT) imaging modality to evaluate the morphology of the mandibular condyle and glenoid fossa in a selected population and document any morphometric changes. Setting and Design It is an observational study. Materials and Methods A retrospective CBCT analysis was performed on 119 patients. The length, width, height, linear measurements of the joint spaces (anterior, posterior, and superior), volume of the condyle, and roof of glenoid fossa thickness were evaluated on both the left and right sides in both males and females. Results The height, width, and length of mandibular condyle were significantly increased in males on both sides. Except for the left anterior space, all other spaces were significantly larger in males. Overall, the volume of the condyles in males was significantly increased on both sides. Conclusion CBCT can be a valuable diagnostic aid in the evaluation of various dimensions, joint spaces, and condylar volume in different planes and thus, can be a useful predictor in the assessment of treatment outcomes of disorders affecting the TMJ.

Introduction: Temporomandibular joint disorders (TMDs) involve abnormalities of either the disc or associated muscular structure. Evidence continues to accumulate regarding the untreated diseases of stomatognathic system, in particular, malocclusion and TMDs, which eventually carry a risk of development of postural disorders. The present study was undertaken to assess the correlation between TMDs and altered cervical range of motion and to review its association with the myogenous causes of TMD. Materials and Methods: A total of 80 patients were recruited and were divided into two groups; those diagnosed with TMDs were classified as cases and those who did not suffer from TMDs and/or cervical spine anomalies were classified as controls. Patients reporting with a positive history of painful joints and muscles were examined and were later referred to the department of physiotherapy, where the cervical range of motion was assessed using Baseline® bubble inclinometer. Cervical range of motion in healthy patients was compared with those affected with TMDs using posthoc Tukey test. Results: There was a significant difference in the values for range of motion and was found to be considerably restricted among the TMD subjects. Disability for the range of motion was statistically significant with a P-value of

The most predominant kind of disease that is normal among ladies is breast cancer. It is one of the significant reasons among ladies, regardless of huge endeavors to stay away from it through screening developers. An automatic detection system for disease helps doctors to identify and provide accurate results, thereby minimizing the death rate. Computer-aided diagnosis (CAD) has minimum intervention of humans and produces more accurate results than humans. It will be a difficult and long task that depends on the expertise of pathologists. Deep learning methods proved to give better outcomes when correlated with ML and extricate the best highlights of the images. The main objective of this paper is to propose a deep learning technique in combination with a convolution neural network (CNN) and long short-term memory (LSTM) with a random forest algorithm to diagnose breast cancer. Here, CNN is used for feature extraction, and LSTM is used for extracted feature detection. The experimental results show that the proposed system accomplishes 100% of accuracy, a sensitivity of 99%, recall of 99%, and an F1-score of 98% compared to other traditional models. As the system achieved correct results, it can help doctors to investigate breast cancer easily.

Background: The frequency of occurrence of disasters is on the rise all over the world. Workforce shortage can be a major impediment toward efficient disaster management. Incorporation of other health-care workers along with conventional medical personnel might be critical for efficient and effective management of disasters. Objective: The objective of this study was to assess various aspects pertaining to disaster management among various health-care students in India. Methods: Final-year students pursuing medicine, dentistry, nursing, physiotherapy, pharmacy, Ayurveda, and homeopathy at various institutions in Mangalore, India, were the study participants. Participants' willingness to partake in disaster management and knowledge, attitude, behavior, and perceived effectiveness pertaining to disaster management was ascertained by a questionnaire method. Their previous history of training and familiarity with standard operating procedures was assessed. Results: A total of 437 students belonging to seven health-care institutions participated in the study. Overall, 98.40% of the participants were willing to partake in disaster management. The mean knowledge, attitude, behavior, and perceived effectiveness scores were 49.19%, 81.75%, 47.28%, and 66.20%, respectively. Step-wise multiple linear regression analysis revealed that course (β = 0.247, P < 0.001), attitude (β = 0.154,P = 0.001), and behavior (β = 0.284, P < 0.001) were significant predictors of perceived effectiveness. Conclusions: Participants in the present study revealed that they were willing to partake in disaster management. The participants also reported poor behavior and knowledge scores but appropriate attitude scores. The present study highlights the need for curriculum changes and policy implications for effective integration of various sectors for disaster management, particularly in developing nations such as India, which have a definite scarcity of resources.

Orthohantaviruses are zoonotic pathogens that play a significant role in public health. These viruses can cause haemorrhagic fever with renal syndrome in Eurasia. In the Republic of Kazakhstan, the first human cases were registered in the year 2000 in the West Kazakhstan region. Small mammals can be reservoirs of orthohantaviruses. Previous studies showed orthohantavirus antigens in wild-living small mammals in four districts of West Kazakhstan. Clinical studies suggested that there might be further regions with human orthohantavirus infections in Kazakhstan, but genetic data of orthohantaviruses in natural foci are limited. The aim of this study was to investigate small mammals for the presence of orthohantaviruses by molecular biological methods and to provide a phylogenetic characterization of the circulating strains in Kazakhstan. Small mammals were trapped at 19 sites in West Kazakhstan, four in Almaty region and at seven sites around Almaty city during all seasons of 2018 and 2019. Lung tissues of small mammals were homogenized and RNA was extracted. Orthohantavirus RT-PCR assays were applied for detection of partial S and L segment sequences. Results were compared to published fragments. In total, 621 small mammals from 11 species were analysed. Among the collected small mammals, 2.4% tested positive for orthohantavirus RNA, one sample from West Kazakhstan and 14 samples from Almaty region. None of the rodents caught in Almaty city were infected. Sequencing parts of the small (S) and large (L) segments specified Tula virus (TULV) in these two regions. Our data show that geographical distribution of TULV is more extended as previously thought. The detected sequences were found to be split in two distinct genetic clusters of TULV in West Kazakhstan and Almaty region. TULV was detected in the common vole (Microtus arvalis) and for the first time in two individuals of the forest dormouse (Dryomys nitedula), interpreted as a spill-over infection in Kazakhstan.

Omsk haemorrhagic fever virus (OHFV) is the agent leading to Omsk haemorrhagic fever (OHF), a viral disease currently only known in Western Siberia in Russia. The symptoms include fever, headache, nausea, muscle pain, cough and haemorrhages. The transmission cycle of OHFV is complex. Tick bites or contact with infected small mammals are the main source of infection. The Republic of Kazakhstan is adjacent to the endemic areas of OHFV in Russia and febrile diseases with haemorrhages occur throughout the country—often with unclear aetiology. In this study, we examined human cerebrospinal fluid samples of patients with suspected meningitis or meningoencephalitis with unknown origins for the presence of OHFV RNA. Further, reservoir hosts such as rodents and ticks from four Kazakhstan regions were screened for OHFV RNA to clarify if this virus could be the causative agent for many undiagnosed cases of febrile diseases in humans in Kazakhstan. Out of 130 cerebrospinal fluid samples, two patients (1.53%) originating from Almaty city were positive for OHFV RNA. Screening of tick samples revealed positive pools from different areas in the Akmola region. Of the caught rodents, 1.1% out of 621 were positive for OHFV at four trapping areas from the West Kazakhstan region. In this paper, we present a broad investigation of the spread of OHFV in Kazakhstan in human cerebrospinal fluid samples, rodents and ticks. Our study shows for the first time that OHFV can not only be found in the area of Western Siberia in Russia, but can also be detected up to 1.600 km away in the Almaty region in patients and natural foci.

Objective: Vitamin D deficiency is associated with an unfavorable metabolic profile in observational studies. The intention was to compare insulin sensitivity (the primary end point) and secretion and lipids in subjects with low and high serum 25(OH)D (25-hydroxyvitamin D) levels and to assess the effect of vitamin D supplementation on the same outcomes among the participants with low serum 25(OH)D levels.Research Design and Methods: Participants were recruited from a population-based study (the Tromsø Study) based on their serum 25(OH)D measurements. A 3-h hyperglycemic clamp was performed, and the participants with low serum 25(OH)D levels were thereafter randomized to receive capsules of 20,000 IU vitamin D(3) or identical-looking placebo twice weekly for 6 months. A final hyperglycemic clamp was then performed.Results: The 52 participants with high serum 25(OH)D levels (85.6 ± 13.5 nmol/L [mean ± SD]) had significantly higher insulin sensitivity index (ISI) and lower HbA(1c) and triglycerides (TGs) than the 108 participants with low serum 25(OH)D (40.3 ± 12.8 nmol/L), but the differences in ISI and TGs were not significant after adjustments. After supplementation, serum 25(OH)D was 142.7 ± 25.7 and 42.9 ± 17.3 nmol/L in 49 of 51 completing participants randomized to vitamin D and 45 of 53 randomized to placebo, respectively. At the end of the study, there were no statistically significant differences in the outcome variables between the two groups.Conclusions: Vitamin D supplementation to apparently healthy subjects with insufficient serum 25(OH)D levels does not improve insulin sensitivity or secretion or serum lipid profile. [ABSTRACT FROM AUTHOR]

BackgroundIn Kazakhstan, a live plague vaccine EV 76 NIIEG has been used for plague prophylaxis since the mid-1930s. Vaccination is administered yearly among people living in plague-enzootic areas. Similar practices are used in other former Soviet Union countries. Yet, to this day, the effectiveness period of the vaccine is unknown. It is also not clear how different factors can affect the effectiveness of the vaccine over time.MethodsWe surveyed changes in antibody levels specific for F1 antigens of Yersinia pestis among vaccinated people 4, 8, and 12 months post- vaccination. Blood samples were taken from the participants of the study for producing sera, which was later analyzed using indirect hemagglutination reaction with antigenic erythrocyte assay (micromethod) for identifying antibodies to F1 Y.pestis.ResultsIn first-time-receivers of the plague vaccine, antibody titer reached the highest level of antibody that represents a conditionally protective titer after 4 months, dropped drastically after 8 months, and dropped again after 12 months. Similar results were obtained among those who have been vaccinated previously. However, in that group, the percentage of people with a level of antibody that represents a conditionally protective titer remained statistically significant even after 8 and 12 months.ConclusionBased on the results of this study, we recommend initiating vaccination campaigns for the medical and veterinary staff, as well as the general population four months prior to the springtime epizootics of plague among wild rodents.

In current study, the effect of gibberellic acid was tested for production of biomass, polyphenolics and Steviol glycosides in adventitious root cultures of Stevia rebaudiana. Adventitious cultures were induced from the roots of in vitro grown plantlets on Murashige and Skoog (MS) medium containing combination of gibberellic acid (GA3; 0.5, 1.0, 1.5 and 2.0 mg/L) and naphthalene acetic acid (NAA; 0.5 mg/L). Initially, a known mass of inoculum roots were shifted into suspension media augmented with various GA3 concentrations. The growth behavior of adventitious roots was recorded every 3 days for a period of 30 days. Maximum biomass biosynthesis (13.12 g/flask) was noticed in exponential phase on 27th day in the suspension containing 2.0 mg/L of GA3. Other GA3 concentrations also displayed optimum patterns of biomass accumulation as compared to the control. Adventitious roots were investigated for total phenolic content (TPC) and production (TPP), total flavonoid content (TFC) and production (TFP), and 1, 1-diphenyl-2-picrylhydrazyl (DPPH)-based antioxidant potential. Maximum phenolics (TPC 9.84 mg gallic acid equivalent (GAE)/g-dry weight (DW)) and TPP (147.6 mg/L), TFC (5.12 mg Quercitin equivalent (QE)/g-DW) and TFP (76.91 mg/L) were observed in 2.0 mg/L GA3 treated cultures. The same concentration of gibberellic acid enhanced antioxidant activity (77.2%). Furthermore, maximum stevioside (7.13 mg/g-DW), rebaudioside-A (0.27 mg/g-DW) and dulcoside-A (0.001 mg/g-DW) were observed in roots exposed to 2.0 mg/L GA3. This is the first report on the application of GA3 on biomass accumulation and secondary metabolite production in S. rebaudiana. The current study will be helpful to scale up the adventitious root cultures in bioreactors for the production of biomass and pharmaceutically important secondary metabolites.

Introduction: Global Smokeless Tobacco (SLT) consumption is on the rise and constitutes a major Public Health problem. Controlling SLT intake is central to containing the increasing tobacco menace. Aim: The present study was undertaken to comprehensively explore various factors involved in SLT consumption and its cessation among current SLT users. Materials and Methods: Present study was conducted among current SLT users visiting Department of Oral Medicine and Radiology, Manipal College of Dental Sciences (MCODS), Manipal University, Mangalore, Karnataka, India. A structured, pretested and self-administered questionnaire was employed for the present study. Knowledge, attitude, behaviour, worksite practices of respondents towards SLT consumption and its cessation, barriers to SLT cessation were explored. Information about socio-demographic variables was also collected. Results: Overall, 170 current SLT users participated in the present study. Results revealed that the mean knowledge, attitude, worksite related practices and barrier scores were 9.96(55.33%), 48.89(81.48%), 2.70(33.75%) and 54.25(60.27%) respectively. Correlation analysis revealed significant association of socio-demographic factors with knowledge, attitude and worksite related practices (p

Introduction: Recognition of sex is an important aspect of identification of an individual. Apart from pelvis, skull exhibits highest sexual dimorphism in the human body- Lateral cephalograms are an invaluable tool in identification of sex as they reveal architectural and morphological details of the skull on a single radiograph- The equipment required for lateral cephalometry is readily available and the technique is cost-effective, easy to perform, offers quick results, reproducible and can be implemented in any special training for the forensic examiner. The present study was undertaken to evaluate the role of lateral cephalograms and the nine cephalometric variables in the identification of sex and also to derive a discriminant function equation for identification of sex. Materials and methods: A total of 100 lateral cephalograms were taken of 50 male and 50 female subjects aged between 25 and 54 years belonging to South Indian population. The nine derived cephabmetnc parameters were used to arrive at a discriminant function equation which was further assessed for its reliability among the study subjects. Results: Among nine cephalometric parameters used, seven were reliable in the identification of sex. The derived discriminant function equation accurately identified 88% of the male study subjects as males and 84% of the female subjects as females. Conclusion: The lateral cephalograms and the nine cephalometric variables employed in the study are simple and reliable tools of sexual discrimination. The derived discriminant functional equation can be used to accurately identify sex of an individual belonging to South Indian population

The synthesis of 6-azidomethyl-5,6,7,8-tetrahydropterin (6-AzmH4Ptr) (9) starting from 2,4-diamino- 6-hydroxymethylpteridine (1) is described. A special protecting group strategy had to be applied to perform the structural modifications. The introduction of the azido function was achieved by a Mitsunobu reaction converting the N2 - N ,N -dimethylaminomethylen-6 -hydroxymethyl-5-pivaloyl-5,6,7 ,8-tetrahydropterin (7) with diphenylphosphoryl azide into the corresponding 6-azidomethyl derivative (8). The newly synthesized compounds have been characterized by elemental analyses, UV, IR and 1H-NMR spectra. The photolysis of 6-AzmH4Ptr (9) and its inactivation effect upon aromatic amino acid mono oxygenases has been studied

Purpose: The SWENOTECA-MIR prospective multicenter study aims to assess the clinical value of miR-371a-3p as a novel marker in metastatic germ cell tumor patients undergoing retroperitoneal lymph node dissection (RPLND), to predict the presence of viable residual tumor., Materials and Methods: A total of 114 patients (86 nonseminomas, 28 seminomas) who underwent surgery for presumed metastatic disease pre chemotherapy (primary RPLND) and post chemotherapy RPLND were included. The expression of miR-371a-3p was evaluated using reverse transcription-digital droplet polymerase chain reaction before and after RPLND. Pre- and postoperative miR-371a-3p levels were statistically compared, and optimism-corrected performance calculations compared with conventional serum tumor markers. Associations were evaluated by logistic regression. Patients who underwent primary RPLND were categorized into seminoma and nonseminoma groups., Results: Among the seminoma patients (n = 24) undergoing primary RPLND, all had normal conventional markers. Six patients received adjuvant treatment before surgery. miR-371a-3p exhibited a sensitivity of 74%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 21% for viable tumor. The levels of miR-371a-3p significantly decreased after surgery. In the nonseminoma group (n = 18) treated with primary RPLND, 22% had elevated conventional markers and 3 had received prior adjuvant treatment. miR-371a-3p showed a sensitivity of 34%, specificity of 88%, positive predictive value of 67%, and negative predictive value of 62% for the primary nonseminoma patients. No association was observed between stage or prior adjuvant treatment and the outcome of the miR test. In the postchemotherapy group (n = 72), the miR-371a-3p sensitivity was 9%, reducing to 0 when excluding patients with seminoma (n = 4). Teratomas and benign histology were essentially negative., Conclusions: Our study highlights miR-371a-3p as a fairly sensitive and highly specific marker for prechemotherapy seminomas, outperforming conventional markers. However, in prechemotherapy nonseminomas as well as in postchemotherapy patients, we observed low sensitivity and no significant differences in miR-371a-3p levels before and after surgery, suggesting limited utility for miR-371a-3p in this context.

Purpose: The aromatase inhibitor letrozole and the aromatase inactivator exemestane are two of the most pivotal cancer drugs used for endocrine treatment of ER-positive breast cancer in all phases of the disease. Although both drugs inhibit CYP19 (aromatase) and have been used for decades, a direct head-to-head, intra-patient-cross-over comparison of their ability to decrease estrogen synthesis in vivo is still lacking., Methods: Postmenopausal breast cancer patients suitable for neoadjuvant endocrine therapy were randomized to receive either letrozole (2.5 mg o.d.) or exemestane (25 mg o.d.) for an initial treatment period, followed by a second treatment period on the alternative drug (intra-patient cross-over study design). Serum levels of estrone (E1), estradiol (E2), letrozole, exemestane, and 17-hydroxyexemestane were quantified simultaneously using a novel, ultrasensitive LC-MS/MS method established in our laboratory., Results: Complete sets of serum samples (baseline and during treatment with letrozole or exemestane) were available from 79 patients, including 40 patients starting with letrozole (cohort 1) and 39 with exemestane (cohort 2). Mean serum estrone and estradiol levels in cohort 1 were 174 pmol/L and 46.4 pmol/L at baseline, respectively. Treatment with letrozole suppressed serum E1 and E2 to a mean value of 0.2 pmol/L and 0.4 pmol/L (P < 0.001). After the cross-over to exemestane, mean serum levels of E1 and E2 increased to 1.4 pmol/L and 0.7 pmol/L, respectively. In cohort 2, baseline mean serum levels of E1 and E2 were 159 and 32.5 pmol/L, respectively. Treatment with exemestane decreased these values to 1.8 pmol/L for E1 and 0.6 pmol/L for E2 (P < 0.001). Following cross-over to letrozole, mean serum levels of E1 and E2 were significantly further reduced to 0.1 pmol/L and 0.4 pmol/L, respectively. Serum drug levels were monitored in all patients throughout the entire treatment and confirmed adherence to the protocol and drug concentrations within the therapeutic range for all patients. Additionally, Ki-67 values decreased significantly during treatment with both aromatase inhibitors, showing a trend toward a stronger suppression in obese women., Conclusion: To the best of our knowledge, we present here for the first time a comprehensive and direct head-to-head, intra-patient-cross-over comparison of the aromatase inhibitor letrozole and the aromatase inactivator exemestane concerning their ability to suppress serum estrogen levels in vivo. All in all, our results clearly demonstrate that letrozole therapy results in a more profound suppression of serum E1 and E2 levels compared to exemestane., (© 2024. The Author(s).)

This study aimed to register and analyse outcomes after iatrogenic ureteral injuries (IUI) with special emphasis on potential consequences of a delayed diagnosis, and further to analyse if the incidence of IUI has changed during the study period. 108 patients treated for an IUI during 2001-2021 were included. Injuries due to endourological procedures, planned tumour resection and traumatic injuries were excluded. All relevant information to answer the research questions were entered into a database. Chi-square and t-tests were used for categorical and continuous variables respectively. Regression analysis was used to evaluate potential change of incidence in IUIs over time. Our results showed that most IUIs (74, 69%) were caused by gynaecological surgery. 49 (45%) had a delayed diagnosis (not diagnosed intraoperatively). Younger age (mean 50 vs 62 years, p < 0.001) and benign indication for laparoscopic hysterectomy (OR 8.0, p < 0.001) predisposed for a delayed diagnosis. Patients with a delayed diagnosis had a higher number of secondary injury related procedures (mean 4.6 vs 1.7, p < 0.001), hospital admissions (mean 3.0 vs 0.8, p < 0.001) and longer hospital stays (mean 20.6 vs 3.9 days p < 0.001) compared to patients with an intraoperative diagnosis. There was complete recovery for 91% of the patients. We did not observe any changes in IUI incidence during the study period. In conclusion, our study underlines that IUI can cause major morbidity for the patient affected if not diagnosed intraoperatively. Benign indication and younger age are predictors for a delayed diagnosis. The prognosis is good, with 91% full recovery. No significant changes in incidence of IUIs were observed., (© 2024. The Author(s).)

Background and Objective: There is an unmet need to avoid long-term morbidity associated with standard cytotoxic treatment for low-volume metastatic seminoma. Our aim was to assess the oncological efficacy and surgical safety of retroperitoneal lymph node dissection (RPLND) as treatment in a population-based cohort of metastatic seminoma patients with limited retroperitoneal lymphadenopathy., Methods: Sixty-two seminoma patients in Norway and Sweden were included in the cohort from 2019 to 2022. Patients with lymphadenopathy ≤3 cm, having primary clinical stage (CS) IIA/B or CS I with a relapse, were operated with uni- or bilateral template RPLND, open or robot assisted. The outcome measures included surgical complications as per Clavien-Dindo, and Kaplan-Meier survival estimates for 24-mo progression-free survival (PFS) and overall survival (OS)., Key Findings and Limitations: In the cohort, 33 (53%) had CS I with a relapse during surveillance, six (10%) CS I with a relapse following adjuvant chemotherapy, and 23 (37%) initial CS IIA/B. Metastatic seminoma was verified in 58 patients (94%) with a median largest diameter of 18 mm (interquartile range [IQR] 13-24). Robot-assisted RPLND was performed in 40 patients (65%). Clavien-Dindo III complications were observed in three patients (5%); no grade ≥IV complications occurred. Eighteen patients (29%) received adjuvant chemotherapy after surgery. The median follow-up was 23 mo (IQR 16-30), and recurrence occurred in six patients (10%) after a median of 8 mo (IQR 4-14). PFS was 90% (95% confidence interval: 0.86-1) and OS was 100% at 24 mo., Conclusions and Clinical Implications: RPLND as primary treatment is an option for selected low-stage seminomas with a limited burden of disease, showing low complications and low relapse rates, with the potential to reduce long-term morbidity., Patient Summary: In seminoma patients with limited metastatic spread, surgery is a treatment option offering an alternative to chemotherapy or radiation. This paper covers the first 62 patients operated in Norway and Sweden., (© 2024 The Author(s).)

Objectives: To assess whether extended surveillance with repeated computed tomography (CT) scans for patients with clinical stage IIA (CS IIA; <2 cm abdominal node involvement) and negative markers (Mk-) non-seminomatous germ cell tumours (NSGCTs) can identify those with true CS I. To assess the rate of benign lymph nodes, teratoma, and viable cancer in retroperitoneal lymph node dissection (RPLND) histopathology for patients with CS IIA Mk- NSGCT., Patients and Methods: Observational prospective population-based study of patients diagnosed 2008-2019 with CS IIA Mk- NSGCT in the Swedish and Norwegian Testicular Cancer Group (SWENOTECA) registry. Patients were managed with surveillance, with CT scans, and tumour markers every sixth week for a maximum of 18 weeks. Patients with radiological regression were treated as CS I, if progression with chemotherapy, and remaining CS IIA Mk- disease with RPLND. The end-point was the number and percentage of patients down-staged to CS I on surveillance and rate of RPLND histopathology presented as benign, teratoma, or viable cancer., Results: Overall, 126 patients with CS IIA Mk- NSGCT were included but 41 received therapy upfront. After surveillance for a median (range) of 6 (6-18) weeks, 23/85 (27%) patients were in true CS I and four (5%) progressed. Of the remaining 58 patients with lasting CS IIA Mk- NSGCT, 16 received chemotherapy and 42 underwent RPLND. The RPLND histopathology revealed benign lymph nodes in 11 (26%), teratoma in two (6%), and viable cancer in 29 (70%) patients., Conclusions: Surveillance with repeated CT scans can identify patients in true CS I, thus avoiding overtreatment. The RPLND histopathology in patients with CS IIA Mk- NSGCT had a high rate of cancer and a low rate of teratoma., (© 2024 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Background: Ureteropelvic junction obstruction (UPJO) is characterised by stenosis of the ureteral lumen at the level of the renal pelvis and proximal ureter. At Haukeland University Hospital, robotic-assisted laparoscopic pyeloplasty (RLP) for UPJO has been performed since 2014. The aim of this study was to evaluate the results of the treatment and consider what determines treatment success., Materials and Methods: Retrospective review was performed of consecutive patients undergoing RLP between 2014-2022. Outcomes of interest included symptom relief, complication rates and renographic findings at follow-up. Treatment success was defined in terms of symptom improvement and/or improvement as well as relief of obstruction on renography., Results: In total, 95 RLPs were performed in 54 women and 41 men, with a mean age of 40 years (IQR: 21-58). Flank pain was the most frequent presenting complaint (n = 81, 85%) followed by infection (n = 33, 35%). More than one indication for surgery was present in 1/3 of the patients. Urodynamic relevant obstruction on renography was found in 62 patients (65%) preoperatively. Mean operative time was 123 minutes (range 60-270). Two patients experienced minor intraoperative complications. At three months follow-up, 91% of patients had symptom relief, and no obstruction on renography was recorded in 64%. There was no significant association between improvement in symptoms and renography findings at follow-up, p = 1., Conclusions: RLP can deliver a high success rate in terms of symptom relief and few complications. There was no association between renography findings and symptom relief at follow-up. Success after surgery should be determined by symptom relief rather than renography findings.

Objectives: The aim was to investigate the predictive abilities of a preoperative diffusion-weighted MRI (dwMRI) among patients with surgically treated upper tract urothelial carcinoma (UTUC)., Materials and Methods: Written consent was obtained from all participants in this prospective and ethically approved study. Thirty-five UTUC patients treated with radical surgery were examined with a preoperative dwMRI and prospectively included during 2017-2022. Two radiologists examined the CT scans and dwMRIs for radiological stage, and the apparent diffusion coefficient (ADC) in the tumours at the dwMRI was registered. The radiologists were blinded for patient history, final histopathology and the readings of the other radiologist. The radiological variables were analysed regarding their abilities to predict muscle-invasive disease (MID, T2-T4) and tumour grade at final pathology after radical surgery. The predictive abilities were assessed using chi-square tests, Student's t -test and calculating the area under the curve in a receiver operating characteristic (ROC) curve. Correlation between the two radiologists was quantified calculating the intra-class correlation coefficient. P -values <0.05 were considered statistically significant., Results: Mean age was 72 years, 20 had high-grade tumour, and 13 patients had MID. The ADC values at the dwMRI were significantly lower among patients with MID compared to patients with non-muscle-invasive disease (930 vs 1189, p  = <0.001). The area under the ROC curve (AUC) in an ROC curve to predict MID was 0.88 (CI 0.77-0.99, p  = <0.001). The ADC values were significantly lower among patients with high-grade tumours compared to low-grade tumours (1005 vs 1210, p  = 0.002). The correlation of the ADC measurements between the two radiologists was of 0.93 (CI 0.85-0.96, p  < 0.001)., Conclusion: Tumour ADC at the MRI emerges as a potential biomarker for aggressive disease. The results are promising but should be validated in a larger, multicentre study., Competing Interests: None., (© 2024 The Authors. BJUI Compass published by John Wiley & Sons Ltd on behalf of BJU International Company.)

Context: Longitudinal data regarding vitamin D status in adolescence is scarce. This study presents population-based data from an Arctic adolescent population (n = 589) at 16 and 18 years., Objective: The aims of this study were to investigate changes in vitamin D status during 2 years in adolescence, and whether lifestyle changes were associated with serum 25-hydroxyvitamin D (s-25(OH)D) at follow-up., Methods: Fit Futures is a longitudinal study at 69°N in Norway. Participants had their s-25(OH)D levels analyzed in their first and third year of upper secondary school (median age 16 and 18 years), in Fit Futures 1 (FF1) and Fit Futures 2 (FF2), respectively. Self-reported lifestyle habits were registered through questionnaires. The association between lifestyle changes and s-25(OH)D levels at follow-up were calculated by regression analyses, controlling for baseline s-25(OH)D levels., Results: Longitudinal data were available for 309 girls and 280 boys. The proportion of adolescents with s-25(OH)D <50 nmol/L were 73.7% in FF1 and 77.1% in FF2, while the proportion <30 nmol/L constituted 35.7% in FF1 and 40.9% in FF2. Of those with s-25(OH)D <30 nmol/L (severe vitamin D deficiency) in FF1, 73.3% remained severely deficient in FF2. Among boys, an increase in UV exposure was significantly associated with higher s-25(OH)D levels in FF2 (beta; CI [nmol/L] 12.9; 9.1, 16.7). In girls, decreased vitamin/mineral supplement intake was significantly associated with lower s-25(OH)D at FF2 (-6.7; -10.2, -3.1), while increased UV (10.8; 7.0, 14.7) and combined hormonal contraceptive exposure (12.1; 6.0, 18.1) in FF2 was significantly associated with higher s-25(OH)D levels in FF2., Conclusion: Severe vitamin D deficiency was prevalent throughout adolescence. Lifestyle changes may alter s-25(OH)D levels in this age group., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Per- and polyfluoroalkyl substances (PFAS) comprise a large group of chemicals that are ubiquitous in the environment and include recognized persistent organic pollutants. The aim of this cross-sectional study was to investigate possible endocrine disrupting effects of different PFAS in adolescents., Methods: Serum concentrations of PFAS, thyroid, parathyroid and steroid hormones were measured in 921 adolescents aged 15-19 years in the Fit Futures study, Northern Norway. The questionnaire included data on self-reported age at menarche and puberty development score (PDS). Multiple linear and logistic regression analyses and principle component analyses (PCA) were used to assess associations of PFAS with hormones concentrations and puberty indices., Results: In girls, total PFAS (∑PFAS), perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), perfluorodecanoate (PFDA) were positively associated with dehydroepiandrosterone sulfate (DHEAS) and negatively associated with 11-deoxycorticosterone (11-DOC)/DHEAS ratio. In boys, the associations with 11-DOC/DHEAS ratio were positive for ∑PFAS, perfluoroheptanoate (PFHpA), perfluoroheptane sulfonate (PFHpS), PFOA, and PFOS. Perfluoroundecanoate (PFUnDA) was negatively associated with free thyroxine (fT4) and free triiodothyronine (fT3) in boys. PFNA and PFDA were also negatively associated with fT3 in boys. Serum parathyroid hormone concentration (PTH) was negatively associated with ∑PFAS and perfluorohexane sulfonate (PFHxS) in girls, and with PFOS in boys. PFDA and PFUnDA were positively associated with early menarche, while ∑PFAS and PFOA were positively associated with PDS in boys. No associations of PFAS with serum testosterone, follicle-stimulating hormone, or luteinizing hormone were found in either sex. In girls, PFOA was positively associated with free testosterone index (FTI). In boys, PFOA was positively associated with androstendione and 17-OH-progesterone, while PFHpA was positively associated with estradiol., Conclusions: Serum concentrations of several PFAS were associated with parathyroid and steroid hormones in both sexes, and with thyroid hormones in boys, as well as with early menarche in girls and higher PDS in boys., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Objective: To validate Vergouwe's prediction model using the Swedish and Norwegian Testicular Cancer Group (SWENOTECA) RETROP database and to define its clinical utility., Materials and Methods: Vergouwe's prediction model for benign histopathology in post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) uses the following variables: presence of teratoma in orchiectomy specimen; pre-chemotherapy level of alpha-fetoprotein; β-Human chorionic gonadotropin and lactate dehydrogenase; and lymph node size pre- and post-chemotherapy. Our validation cohort consisted of patients included in RETROP, a prospective population-based database of patients in Sweden and Norway with metastatic nonseminoma, who underwent PC-RPLND in the period 2007-2014. Discrimination and calibration analyses were used to validate Vergouwe's prediction model results. Calibration plots were created and a Hosmer-Lemeshow test was calculated. Clinical utility, expressed as opt-out net benefit (NB opt-out ), was analysed using decision curve analysis., Results: Overall, 284 patients were included in the analysis, of whom 130 (46%) had benign histology after PC-RPLND. Discrimination analysis showed good reproducibility, with an area under the receiver-operating characteristic curve (AUC) of 0.82 (95% confidence interval 0.77-0.87) compared to Vergouwe's prediction model (AUC between 0.77 and 0.84). Calibration was acceptable with no recalibration. Using a prediction threshold of 70% for benign histopathology, NB opt-out was 0.098. Using the model and this threshold, 61 patients would have been spared surgery. However, only 51 of 61 were correctly classified as benign., Conclusions: The model was externally validated with good reproducibility. In a clinical setting, the model may identify patients with a high chance of benign histopathology, thereby sparing patients of surgery. However, meticulous follow-up is required., (© 2023 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Metastatic castration-resistant prostate cancer (mCRPC) is an immunologically cold disease with dismal outcomes. Cryoablation destroys cancer tissue, releases tumor-associated antigens and creates a pro-inflammatory microenvironment, while dendritic cells (DCs) activate immune responses through processing of antigens. Immunotherapy combinations could enhance the anti-tumor efficacy. This open-label, single-arm, single-center phase I trial determined the safety and tolerability of combining cryoablation and autologous immature DC, without and with checkpoint inhibitors. Immune responses and clinical outcomes were evaluated. Patients with mCRPC, confirmed metastases and intact prostate gland were included. The first participants underwent prostate cryoablation with intratumoral injection of autologous DCs in a 3 + 3 design. In the second part, patients received cryoablation, the highest acceptable DC dose, and checkpoint inhibition with either ipilimumab or pembrolizumab. Sequentially collected information on adverse events, quality of life, blood values and images were analyzed by standard descriptive statistics. Neither dose-limiting toxicities nor adverse events > grade 3 were observed in the 18 participants. Results indicate antitumor activity through altered T cell receptor repertoires, and 33% durable (> 46 weeks) clinical benefit with median 40.7 months overall survival. Post-treatment pain and fatigue were associated with circulating tumor cell (CTC) presence at inclusion, while CTC responses correlated with clinical outcomes. This trial demonstrates that cryoimmunotherapy in mCRPC is safe and well tolerated, also for the highest DC dose (2.0 × 10 8 ) combined with checkpoint inhibitors. Further studies focusing on the biologic indications of antitumor activity and immune system activation could be considered through a phase II trial focusing on treatment responses and immunologic biomarkers., (© 2023. The Author(s).)

Context: Hormone reference intervals in pediatric endocrinology are traditionally partitioned by age and lack the framework for benchmarking individual blood test results as normalized z-scores and plotting sequential measurements onto a chart. Reference curve modeling is applicable to endocrine variables and represents a standardized method to account for variation with gender and age., Objective: We aimed to establish gender-specific biomarker reference curves for clinical use and benchmark associations between hormones, pubertal phenotype, and body mass index (BMI)., Methods: Using cross-sectional population sample data from 2139 healthy Norwegian children and adolescents, we analyzed the pubertal status, ultrasound measures of glandular breast tissue (girls) and testicular volume (boys), BMI, and laboratory measurements of 17 clinical biomarkers modeled using the established "LMS" growth chart algorithm in R., Results: Reference curves for puberty hormones and pertinent biomarkers were modeled to adjust for age and gender. Z-score equivalents of biomarker levels and anthropometric measurements were compiled in a comprehensive beta coefficient matrix for each gender. Excerpted from this analysis and independently of age, BMI was positively associated with female glandular breast volume (β = 0.5, P < 0.001) and leptin (β = 0.6, P < 0.001), and inversely correlated with serum levels of sex hormone-binding globulin (SHBG) (β = -0.4, P < 0.001). Biomarker z-score profiles differed significantly between cohort subgroups stratified by puberty phenotype and BMI weight class., Conclusion: Biomarker reference curves and corresponding z-scores provide an intuitive framework for clinical implementation in pediatric endocrinology and facilitate the application of machine learning classification and covariate precision medicine for pediatric patients., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.)

Male sex is associated with higher risk of both colonisation and infection with Staphylococcus aureus (S. aureus). However, the role of sex-steroids in colonisation among men is largely unknown. Thus, the aim of this study was to investigate possible associations between circulating sex-steroids and nasal carriage of S. aureus in a general male population. The population-based Tromsø6 study (2007-2008) included 752 males aged 31-87 years with serum sex-steroids measured by liquid chromatography tandem mass spectrometry and two nasal swab samples for the assessment of S. aureus carriage. Multivariable logistic regression models were used to study the association between sex-steroid concentrations and S. aureus persistent nasal carriage (two positive swabs vs. others), while adjusting for potential confounding factors.S. aureus persistent nasal carriage prevalence was 32%. Among men aged 55 years and above (median age 65 years), there was an inverse dose-response relationship between serum concentration of testosterone and persistent nasal carriage, and carriers had significantly lower mean levels of testosterone (P = 0.028, OR = 0.94 per nmol/l change in testosterone; 95% CI = 0.90-0.98). This association was attenuated when adjusting for body mass index and age (OR = 0.96 per nmol/l change in testosterone; 95% CI = 0.91-1.01). There was no association in the total population. This large population-based study suggests that testosterone levels may be inversely related to S. aureus persistent nasal carriage in older men. Future studies addressing biological mechanisms underlying the male predisposition to S. aureus colonisation and infection may foster preventive interventions that take sex-differences into account.

Context: Currently there are no assays that can simultaneously quantify serum levels of the third-generation aromatase inhibitors (AIs): letrozole, anastrozole, and exemestane, and the ultra-low levels of estrogens in postmenopausal breast cancer patients on AI treatment. Such measurements may be pivotal for the determination of optimal and individualized treatment regimens. We aimed at developing a liquid chromatography-tandem mass spectrometry (MS/MS) method for simultaneous assessment of letrozole, anastrozole, exemestane, and 17-hydroxyexemestane as well as subpicomolar levels of estradiol and estrone., Methods: Internal standards, calibrators, serum samples, and quality controls were in fully automated steps transferred to a deep-well plate for a 2-step liquid-liquid extraction. The extracts were reconstituted and analytes were separated chromatographically using 2 serially coupled columns, then subject to MS/MS in electrospray ionization mode. The method was thoroughly validated and is traceable to 2 accredited estrogen methods., Results: The measurement range for estrone and estradiol was 0.2 to 12 000 pmol/L and 0.8 to 13 000 pmol/L, and covered the expected therapeutic range for the AIs. All analytes had a precision of less than or equal to 13%, and accuracies within 100 ± 8%. As proof of concept, AI and estrogen levels were determined in serum samples from postmenopausal breast cancer patients under treatment., Conclusion: We present here an assay suitable for the simultaneous measurement of serum levels of all third-generation AIs and ultra-low levels of estrogens, providing a powerful new tool to study drug efficacy and compliance. The method is highly valuable for postmenopausal patients whose pretreatment estradiol levels are below the threshold of detection for most routine assays, but still require suppression., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: The distribution of retroperitoneal lymph node metastases for patients with nonseminoma and a residual tumour of 10-49 mm in a population-based setting is unknown. This information is needed to justify selection of patients for a unilateral template resection., Objective: To describe the location of retroperitoneal metastases and recurrences in patients with nonseminoma germ cell tumour (NSGCT) with a residual tumour of 10-49 mm., Design, Setting, and Participants: RETROP is a population-based prospective observational mapping study of 213 patients in Sweden and Norway with a retroperitoneal residual tumour of 10-49 mm who underwent postchemotherapy retroperitoneal lymph node dissection for metastatic NSGCT during 2007-2014 with median follow-up of 100 mo. Patients were classified according to the testis primary tumour and the distribution of unilateral or bilateral lymph node metastases (with reference to the aorta) present on pre- and/or postchemotherapy computed tomography (CT) scans., Outcome Measurements and Statistical Analysis: The distribution and rate of teratoma or cancer in unilateral or bilateral retroperitoneal fields and the location and rate of retroperitoneal recurrence were measured., Results and Limitations: In total, 65% of the patients had unilateral retroperitoneal lymph node metastases (RLNMs) on CT scans. Patients with unilateral RLNMs had a low risk of contralateral teratoma or cancer (1.6% for right- and 2.6% for left-sided NSGCT) or retroperitoneal recurrence (0% for right- and 4% for left-sided NSGCT). A weakness of the study is that the pathology specimen could not be fully designated to one specific area for some of the patients., Conclusions: Men with postchemotherapy residual disease of 10-49 mm and unilateral metastases on pre- and postchemotherapy CT scans have a low risk of contralateral disease and should be considered for a unilateral template resection., Patient Summary: The surgeon can use computed tomography (CT) scans in deciding on the extent of lymph node dissection in patients with testicular cancer., (Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: To register all cases of urothelial cancer and renal cell carcinoma (RCC) in Norway during 1999-2018 to obtain the contemporary incidence of UTUC and UTUC incidence relative to other urothelial cancers and RCC. Further to analyse possible changes over time regarding UTUC incidence, UTUC patient characteristics, tumour characteristics and survival., Methods: 3502 cases registered with ICD code C65 and C66 during 1999-2018 at the Norwegian cancer registry were entered into a database. After a selection process 3096 cases were included in the study. The crude incidences of UTUC were calculated for each year adjusting for the corresponding population data. Age-standardized rates adjusting to the European standard population (2013) were calculated. Comparisons were made with other cases of urothelial cancer and RCC. For changes over time, the material was split into 5-year periods. Regression analysis was used to calculate yearly changes and for assessing statistical significance. Survival outcomes were calculated using the Kaplan-Meier method., Results: The overall age-standardized incidence rate was 3.88, increasing from 3.21 to 4.70 from first to last 5-year periods. The increase affected all ages except those < 60 years of age, and were observed regardless of gender or anatomical location. UTUC constituted 11.8% of all urothelial cancers, increasing from 9.9 to 12.8%. Mean patient age at diagnosis increased from 71.5 to 73.4 years. The 5-years Cancer-specific survival improved from 57.4 to 65.4%., Conclusion: The incidence of UTUC was higher than expected and increasing. Patient age at diagnosis was increasing., (© 2021. The Author(s).)

Purpose: Intensified treatment such as extended lymph node dissection (LND) and/or perioperative chemotherapy in addition to radical nephroureterectomy (RNU) has been suggested for high-risk cases of upper tract urothelial carcinoma (UTUC). We aimed to identify preoperative predictors of tumour stage and prognosis in the diagnostic work-up before RNU. Further to evaluate if our findings could be used in selecting patients for intensified treatment., Patients and Methods: A total of 179 patients treated with RNU for UTUC at Haukeland University Hospital (HUS) and Vestfold Hospital Trust (VHT) during 2005-2017 were included in this retrospective study. All relevant preoperative variables regarding the patient, the CT and the ureteroscopy (URS) were registered and analysed regarding their ability to predict non-organ confined disease (NOCD, pT3+ and/or N+) at final pathology after RNU. The prognosis was assessed calculating survival for the cohort and stratified by preoperative variables., Results: Local invasion and pathological lymph nodes at CT predicted NOCD in uni and multivariate regression analyses (OR 3.36, p =.004 and OR 6.21, p =.03, respectively). Reactive oedema surrounding the tumour (OR 2.55, p =.02), tumour size (4.8 vs. 3.9 cm, p =.006) and high-grade tumour at URS biopsy (OR 3.59, p =.04) predicted NOCD at univariate regression analyses. The 5-year CSS and OS for the entire cohort was 79% and 60%. ECOG, local invasion, pathological lymph nodes and reactive oedema surrounding the tumour at CT predicted CSS., Conclusions: Several variables at the CT predicted both stage and survival. Local invasion at CT seems the most promising feature for selecting patients for intensified treatment.

Background: Diagnosing Cushing syndrome (CS) can be challenging. The 24-hour urine free cortisol (UFC) measurement is considered gold standard. This is a laborious test, dependent on correct urine collection. Late-night salivary cortisol is easier and is used as a screening test for CS in adults, but has not been validated for use in children., Objective: To define liquid chromatography tandem mass spectrometry (LC-MS/MS)-based cutoff values for bedtime and morning salivary cortisol and cortisone in children, and validate the results in children with and without CS., Methods: Bedtime and morning salivary samples were collected from 320 healthy children aged 4 to 16 years. Fifty-four patients from the children's outpatient obesity clinic and 3 children with pituitary CS were used for validation. Steroid hormones were assayed by LC-MS/MS. Cutoff levels for bedtime salivary cortisol and cortisone were defined by the 97.5% percentile in healthy subjects., Results: Bedtime cutoff levels for cortisol and cortisone were 2.4 and 12.0 nmol/L, respectively. Applying these cutoff levels on the verification cohort, 1 child from the obesity clinic had bedtime salivary cortisol exceeding the defined cutoff level, but normal salivary cortisone. All 3 children with pituitary CS had salivary cortisol and cortisone far above the defined bedtime cutoff levels. Healthy subjects showed a significant decrease in salivary cortisol from early morning to bedtime., Conclusions: We propose that bedtime salivary cortisol measured by LC-MS/MS with a diagnostic threshold above 2.4 nmol/L can be applied as a screening test for CS in children. Age- and gender-specific cutoff levels are not needed., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)

Context: Application of ultrasound (US) to evaluate attainment and morphology of glandular tissue provides a new rationale for evaluating onset and progression of female puberty, but currently no hormone references complement this method. Furthermore, previous studies have not explored the predictive value of endocrine profiling to determine female puberty onset., Objective: To integrate US breast staging with hypothalamic-pituitary-gonadal hormone references and test the predictive value of an endocrine profile to determine thelarche., Design Setting and Participants: Cross-sectional sample of 601 healthy Norwegian girls, ages 6 to 16 years., Main Outcome Measures: Clinical and ultrasound breast evaluations were performed for all included girls. Blood samples were analyzed by immunoassay and ultrasensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) to quantify estradiol (E2) and estrone (E1) from the subpicomolar range., Results: References for E2, E1, luteinizing hormone, follicle-stimulating hormone, and sex hormone-binding globulin were constructed in relation to chronological age, Tanner stages, and US breast stages. An endocrine profile index score derived from principal component analysis of these analytes was a better marker of puberty onset than age or any individual hormone, with receiver-operating characteristic area under the curve 0.91 (P < 0.001). Ultrasound detection of nonpalpable glandular tissue in 14 out of 264 (5.3%) girls with clinically prepubertal presentation was associated with significantly higher median serum levels of E2 (12.5 vs 4.9 pmol/L; P < 0.05) and a distinct endocrine profile (arbitrary units; P < 0.001)., Conclusions: We provide the first hormone references for use with US breast staging and demonstrate the application of endocrine profiling to improve detection of female puberty onset., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society.)

Context: Testicular growth represents the best clinical variable to evaluate male puberty, but current pediatric hormone references are based on chronological age and subjective assessments of discrete puberty development stages. Determination of testicular volume (TV) by ultrasound provides a novel approach to assess puberty progression and stratify hormone reference intervals., Objective: The objective of this article is to establish references for serum testosterone and key hormones of the male pituitary-gonadal signaling pathway in relation to TV determined by ultrasound., Design, Setting, and Participants: Blood samples from 414 healthy Norwegian boys between ages 6 and 16 years were included from the cross-sectional "Bergen Growth Study 2." Participants underwent testicular ultrasound and clinical assessments, and serum samples were analyzed by liquid chromatography tandem-mass spectrometry and immunoassays., Main Outcome Measures: We present references for circulating levels of total testosterone, luteinizing hormone, follicle-stimulating hormone, and sex hormone-binding globulin in relation to TV, chronological age, and Tanner pubic hair stages., Results: In pubertal boys, TV accounted for more variance in serum testosterone levels than chronological age (Spearman r = 0.753, P < .001 vs r = 0.692, P < .001, respectively). Continuous centile references demonstrate the association between TV and hormone levels during puberty. Hormone reference intervals were stratified by TV during the pubertal transition., Conclusions: Objective ultrasound assessments of TV and stratification of hormone references increase the diagnostic value of traditional references based on chronological age or subjective staging of male puberty., (© Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Current analytical routine methods lack the sensitivity to monitor plasma estrogen levels in breast cancer patients treated with aromatase inhibitors. Such monitoring is warranted for premenopausal patients treated with an aromatase inhibitor and an LH-releasing hormone analogue in particular. Therefore, we aimed to develop a routine tandem mass spectroscopy combined with liquid chromatography (LC-MS/MS) method for estradiol (E2) and estrone (E1) for use in the sub-picomolar range., Method: Calibrators, quality controls (QC), or serum samples were spiked with isotope-labeled internal standard and purified by liquid-liquid extraction. The reconstituted extracts were analyzed by LC-MS/MS in negative electrospray ionization mode. QCs at 6 levels made from pooled patient sera were used to validate the accuracy, sensitivity, and precision of the method., Results: We achieved limits of quantification of 0.6 pmol/L (0.16 pg/mL) for E2 and 0.3 pmol/L (0.07 pg/mL) for E1. The coefficient of variation was below 9.0% at all QC levels for E2 (range, 1.7-153 pmol/L), and below 7.8% for E1 (range, 1.7-143 pmol/L). The method is traceable to the E2 reference standard BCR576. Reference ranges for E2 and E1 in healthy, postmenopausal women were obtained, for E2: 3.8 to 36 pmol/L, for E1: 22 to 122 pmol/L. We measured and confirmed ultra-low E2 and E1 concentrations in sera from patients on the aromatase inhibitors letrozole or exemestane., Conclusion: This ultrasensitive LC-MS/MS method is suitable for routine assessment of serum E1 and E2 levels in breast cancer patients during estrogen suppression therapy. The method satisfies all requirements for measurement of E2 in the clinical setting as stated by the Endocrine Society in 2013., Precis: We report an ultrasensitive LCMS/MS routine assay that measures pretreatment and suppressed levels of estradiol/estrone during aromatase inhibitor treatment of postmenopausal breast cancer patients., (© Endocrine Society 2020.)

Purpose: Selecting patients for intensified treatment for upper tract urothelial carcinoma can be challenging, partly due to the lack of accurate preoperative staging tools. Several preoperative staging models for upper tract urothelial carcinoma have been presented, but none have been externally validated. The aim of the current study was to perform an external validation of the Margulis nomogram for predicting non-organ-confined upper tract urothelial carcinoma at time of nephroureterectomy., Methods: 209 patients from two high-volume centres in Norway were treated with radical nephroureterectomy during the period 2005-2017. 163 patients with complete data necessary for external validation of the Margulis nomogram were included in the study. All relevant covariates were analysed with uni- and multivariate regression analysis to assess their ability to predict non-organ-confined disease. The Margulis nomogram was applied on the present cohort to calculate predicted risk of non-organ-confined disease. This was compared to the observed risk to assess model calibration. The Margulis nomogram accuracy was measured as the area under the curve in a receiver operator characteristics curve to evaluate model discrimination., Results: Tumour grade (OR 28.1, p = 0.001) and architecture (OR 4.72, p < 0.001) were independent predictors of non-organ-confined disease. There was a high concordance between predicted and observed risk quantified with a Cronbach alpha of 0.96. The Margulis nomogram had an area under the curve of 0.83 in predicting non-organ-confined disease when applied on the current cohort., Conclusions: We consider the Margulis nomogram validated for clinical use.

Suboptimal vitamin D status is common among humans, and might increase bone resorption with subsequent negative effects on bone health. Fatty fish, including Atlantic salmon, is an important dietary vitamin D source. However, due to a considerable change in fish feed composition, the contribution of vitamin D from salmon fillet has been reduced. The main objective was to investigate if intake of vitamin D3 enriched salmon or vitamin D3 tablets decreased bone biomarkers (urinary N-telopeptides, deoxypyridinoline, serum bone-specific alkaline phosphatase, and osteocalcin) compared to a low vitamin D3 intake. The 122 healthy postmenopausal women included in this 12 weeks intervention trial were randomized into four groups: three salmon groups (150 grams/two times/week) and one tablet group (800 IU vitamin D and 1000 mg calcium/day). The salmon groups also received calcium supplements. The salmon had three different vitamin D3/vitamin K1 combinations: high D3+high K1, low D3+high K1, or high D3+low K1. Increased intake of salmon containing high levels of vitamin D3 (0.35-0.38 mg/kg/fillet) and supplements with the same weekly contribution had a positive influence on bone health as measured by bone biomarkers in postmenopausal women. Consequently, an increased level of vitamin D3 at least to original level in feed for salmonids will contribute to an improved vitamin D3 status and may improve human bone health.

Objective The aim of this study was to analyse the results regarding survival, recurrence and kidney preservation after endoscopic treatment for upper urinary tract urothelial carcinoma (UTUC) in a Norwegian hospital during the period from 2001 to 2012, and compare them with results reported in the literature. A further aim was to re-examine all initial histopathological specimens, and stratify primary results according to the World Health Organization/International Society of Urological Pathology grading system of urothelial carcinoma from 2004. Materials and methods Forty-three patients were treated endoscopically with curative intent for UTUC during 2001-2012. Of these, 28 patients were candidates for nephroureterectomy (CNU) with an elective indication, while 15 were non-candidates for nephroureterectomy (NCNU). Analyses were performed separately for the CNU and NCNU groups. Results In the CNU group, the 5 year overall and disease-specific survival (OS and DSS) were 71% and 94%, respectively. In the NCNU group, the OS and DSS were 25% and 41%, respectively. Histopathological verification was available in 40 patients (93%), and re-examination showed 27 low-grade and 13 high-grade tumours. In patients with a low-grade tumour, the OS and DSS were 75% and 96%, respectively. In patients with a high-grade tumour, the OS and DSS were 23% and 39%, respectively. The 5 year kidney protection rate was 51% in the CNU group. The 5 year recurrence-free survival was 72%. Conclusions The endoscopic treatment of UTUC is feasible and safe in histopathologically verified low-grade tumours. The endoscopic treatment of high-grade tumours has poor results, and must be reserved for patients where nephroureterectomy is truly contraindicated.

Aim: The aim was to study vitamin D status in a healthy adolescent Norwegian population at 69°N., Methods: The data presented come from The Tromsø Study: Fit Futures, during the school year 2010/2011 (not including the summer months), where 1,038 (92% of those invited) participated. Physical examinations, questionnaires and blood samples were collected, and serum 25-hydroxyvitamin D (25(OH)D) were analyzed using LC-MS/MS., Results: RESULTS are presented from 475 boys and 415 girls (15-18 years old) with available blood samples. A total of 60.2% had vitamin D deficiency or insufficiency (serum 25(OH)D <50 nmol/l), 16.5% were deficient (<25 nmol/l) and 1.6% had severe vitamin D deficiency (<12.5 nmol/l). Only 12.4% had levels >75 nmol/l. A significant gender difference with a mean (SD) serum 25(OH)D level of 40.5 (20.5) nmol/l in boys and 54.2 (23.2) nmol/l in girls (p <0.01) was present. Furthermore, 51.3% of girls had levels >50 nmol/l in comparison to 29.7% of boys (p <0.01). There was an inverse correlation between parathyroid hormone levels and 25(OH)D, rs= -0.30 (p<0.01). Explanatory factors that were significantly associated with serum 25(OH)D levels in multivariate models were use of snuff, consumption of vitamin D fortified milk, cod liver oil and vitamin/mineral supplements, physical activity, sunbathing holiday and use of solarium in boys, and vitamin/mineral supplements, physical activity, sunbathing holiday and use of solarium in girls ., Conclusions: Vitamin D deficiency is prevalent during the school year among adolescents in northern Norway, particularly among boys., (© 2014 the Nordic Societies of Public Health.)

Bone remodeling is a continuous process regulated by several hormones such as estrogens and parathyroid hormone (PTH). Here we investigated the influence of PTH on estrogen receptor alpha (ERα)-dependent transcriptional activity in MC3T3-E1 osteoblasts. Cells that were transfected with an ER-responsive reporter plasmid and treated with PTH showed increased luciferase activity. However, in the presence of 17β-estradiol, we observed that PTH inhibited ERα-mediated transcription. cAMP mimicked the effects by PTH, and the findings were confirmed in COS-1 cells transfected with expression vector encoding the catalytic subunit of cAMP-dependent protein kinase (PKA). Furthermore, PTH exhibited specific effects on the mRNA expression of the decoy receptor osteoprotegerin (OPG) and the receptor activator of NF kappa-B ligand (RANKL) in MC3T3-E1 osteoblasts. In the absence of 17β-estradiol, PTH and cAMP enhanced the OPG/RANKL ratio, whereas, OPG/RANKL was suppressed when estradiol was present. In conclusion, our results indicate that the presence of estradiol determines whether PTH and cAMP stimulates or inhibits ERα-dependent activity and the OPG/RANKL mRNA expression in an osteoblastic cell line., (Copyright © 2014 Elsevier Inc. All rights reserved.)