Primary Retroperitoneal Lymph Node Dissection as Treatment for Low-volume Metastatic Seminoma in a Population-based Cohort: The Swedish Norwegian Testicular Cancer Group Experience.

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.

Ablative or Surgical Treatment for Small Renal Masses (T1a): A Single-Center Comparison of Perioperative Morbidity and Complications.

The purpose of this study is to evaluate the treatment safety of thermal ablation compared to surgical treatment of T1a tumors (small renal masses) at a high-volume center. We conducted an observational single-center study based on data collected form the National Swedish Kidney Cancer Register (NSKCR) between 2015 and 2021. In total, 444 treatments of T1a tumors were included. Patients underwent surgery (partial or total nephrectomy) or ablative treatment-radiofrequency ablation (RFA) or microwave ablation (MWA). Patient characteristics were retrieved from patient records, and tumor complexity was estimated from pre-interventional CT scans. The odds ratio (OR) of suffering from a severe surgical complication following ablative treatment was estimated using a logistic regression model adjusted for age, BMI, ASA physical status classification, smoking status and RENAL nephrometry score. The frequency of severe surgical complications was 6.3% (16/256 treatments) after surgical intervention and 2.1% (4/188 treatments) following ablative treatment. Our primary hypothesis that ablative treatment is associated with a lower risk of severe surgical complications is supported by the results (OR 0.39; 0.19-0.79; p = 0.013). When adjusting for age, smoking status, ASA score, BMI score and RENAL nephrometry score, we see an even greater difference between the two groups (OR 0.34; 0.17-0.68; p = 0.002). Our study was limited by the differences in patient and tumor characteristics between the two compared groups and the study design. If oncological outcomes are found to be comparable, ablative treatment should be considered as a first-line treatment for all small renal masses.

Isoallopregnanolone Inhibits Estrus Cycle-Dependent Aggressive Behavior.

Among female rats, some individuals show estrus cycle-dependent irritability/aggressive behaviors, and these individual rats may be used as a model for premenstrual dysphoric disorder (PMDD). We wanted to investigate if these behaviors are related to the estrus cycle phase containing moderately increased levels of positive GABA-A receptor-modulating steroids (steroid-PAM), especially allopregnanolone (ALLO), and if the adverse behavior can be antagonized. The electrophysiology studies in this paper show that isoallopregnanolone (ISO) is a GABA-A-modulating steroid antagonist (GAMSA), meaning that ISO can antagonize the agonistic effects of positive GABA-A receptor-modulating steroids in both α1ß2γ2L and α4ß3δ GABA-A receptor subtypes. In this study, we also investigated whether ISO could antagonize the estrus cycle-dependent aggressive behaviors in female Wistar rats using a resident-intruder test. Our results confirmed previous reports of estrus cycle-dependent behaviors in that 42% of the tested rats showed higher levels of irritability/aggression at diestrus compared to those at estrus. Furthermore, we found that, during the treatment with ISO, the aggressive behavior at diestrus was alleviated to a level comparable to that of estrus. We noticed an 89% reduction in the increase in aggressive behavior at diestrus compared to that at estrus. Vehicle treatment in the same animals showed a minimal effect on the diestrus-related aggressive behavior. In conclusion, we showed that ISO can antagonize Steroid-PAM both in α1ß2γ2L and α4ß3δ GABA-A receptor subtypes and inhibit estrus cycle-dependent aggressive behavior.

Prediction of Overall Survival by Thymidine Kinase 1 Combined with Prostate-Specific Antigen in Men with Prostate Cancer.

Thymidine kinase 1 (TK1) is an intracellular enzyme involved in DNA-precursor synthesis. Increased serum TK1 levels are used as a biomarker in various malignancies. We combined serum TK1 with PSA and evaluated its capacity to predict overall survival (OS) in 175 men with prostate cancer (PCa), detected by screening in 1988-1989 (n = 52) and during follow-up (median 22.6 years) (n = 123). TK1 was measured in frozen serum, age was stratified into four groups, and dates of PCa diagnosis and dates of death were obtained from Swedish population-based registries. The median concentration of TK1 and PSA was 0.25 and 3.8 ng/ml. TK1 was an independent variable of OS. In the multivariate analysis, PSA was not statistically significant in combination with age whereas the significance remained for TK1 + PSA. Measured once, TK1 + PSA predicted a difference of up to 10 years (depending on patient subgroup) in OS at a median of 9 years before PCa diagnosis. The TK1 concentration in 193 controls without malignancies did not differ from that of the PCa patients, hence TK1 was likely not released from incidental PCa. Thus, TK1 in the blood circulation may indicate the release of TK1 from sources other than cancers, nonetheless associated with OS.

Spin-Coated Heterogenous Stacked Electrodes for Performance Enhancement in CMOS-Compatible On-Chip Microsupercapacitors.

Integration of microsupercapacitors (MSCs) with on-chip sensors and actuators with nanoenergy harvesters can improve the lifetime of wireless sensor nodes in an Internet-of-Things (IoT) architecture. However, to be easy to integrate with such harvester technology, MSCs should be fabricated through a complementary-metal-oxide-semiconductor (CMOS) compatible technology, ubiquitous in electrode choice with the capability of heterogeneous stacking of electrodes for modulation in properties driven by application requirements. In this article, we address both these issues through fabrication of multielectrode modular, high energy density microsupercapacitors (MSC) containing reduced graphene oxide (GO), GO-heptadecane-9-amine (GO-HD9A), rGO-octadecylamine (rGO-ODA), and rGO-heptadecane-9-amine (rGO-HD9A) that stack through a scalable, CMOS compatible, high-wafer-yield spin-coating process. Furthermore, we compare the performance of the stack with individual electrode MSCs fabricated through the same process. The individual electrodes, in the presence of 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfony)imide (EMIM-TFSI), demonstrate a capacitance of 38, 30, 36, and 105 µF cm-2 at 20 mV s-1 whereas the fabricated stack of electrodes demonstrates a high capacitance of 280 µF cm-2 at 20 mV s-1 while retaining and enhancing the material-dependent capacitance, charge retention, and power density.

Serum thymidine kinase 1 concentration as a predictive biomarker in prostate cancer.

BACKGROUND: Thymidine kinase 1 (TK1) recycles DNA before cell division. We do not know if baseline blood concentrations of TK1 predict death in prostate cancer within 30 years. Our objective is to determine if there is an association between baseline levels of TK1 and future prostate cancer-specific mortality. METHODS: With a "proof of concept" approach, we performed a nested case-control study among 1782 individuals screened for prostate cancer between 1988 and 1989. The concentration of TK1 was measured in frozen serum from 330 men, 36 of whom have died of prostate cancer. The primary endpoint was prostate cancer-specific mortality and outcomes after 30 years were analyzed using logistic regression modeling odds ratios (Ors). RESULTS: The estimated OR (adjusted for age) for dying from prostate cancer among the men who had a TK1 value in the upper tertile was 2.39 (95% confidence interval 1.02-5.63). The corresponding OR, regardless of the cause of death, was 2.81 (1.24-6.34). CONCLUSIONS: High levels of TK1 predicts death in prostate cancer within 30 years of follow-up.

Association between one-time prostate-specific antigen (PSA) test with free/total PSA ratio and prostate cancer mortality: A 30-year prospective cohort study.

OBJECTIVES: To explore if there is a long-term association between baseline prostate-specific antigen (PSA), including free/total PSA ratio and long-term (30-year) risk for prostate cancer death. SUBJECTS AND METHODS: In all, 1782 men were screened for prostate cancer through PSA analysis. Some years later, frozen plasma samples were used to calculate the ratio of free to total PSA (f/t PSA). At 30-year follow-up, baseline PSA and f/t PSA were compared with recent data extracts from the Swedish Cause of Death Registry and Swedish Cancer Registry. PSA values and f/t PSA values were treated as continuous variables in a multivariable analysis and also stratified according to their distribution and useful clinical thresholds. RESULTS: Risk of death from prostate cancer after 30 years of follow-up was significantly increased with a higher baseline PSA level, with the hazard ratio being 1.04 (95% confidence interval 1.03-1.09) per increase of one unit of PSA. Adding f/t PSA increased the model's ability to discriminate (concordance index 0.84-0.88). Men with PSA levels <1.0 ng/mL had a very low long-term risk of prostate cancer death (1.2% risk). An f/t PSA ≥ 0.25 extended the low-risk range to PSA < 2.0 ng/mL (1.5% risk). CONCLUSION: Prostate-specific antigen testing can be carried out less frequently or can be discontinued in men aged 55-70 years if their PSA levels are <2.0 ng/mL and the f/t PSA is ≥0.25.

Association between dihydrotestosterone and long-term risk for prostate cancer mortality: A prospective cohort study.

BACKGROUND: The androgen metabolism plays an important role in the progression of prostate cancer. Contradictory to what one might assume given the androgenic potency of dihydrotestosterone (DHT) there are indications that high DHT levels protect from prostate cancer. We want to determine whether there is a long-term association between baseline levels of DHT and death from prostate cancer. METHOD: During the years 1988 and 1989, 1782 men out of 2400 invited were screened for prostate cancer. The invited men were randomly selected from a background population of more than 27 000 men. Serum levels of DHT were analyzed for all 65 men diagnosed in the trial and 130 controls from the same cohort without any signs of prostate cancer. In this study we evaluate outcomes for the whole cohort (n = 195), the men without clinical signs of prostate cancer at beginning of follow up (n = 130) and men with screening detected cancer (n = 65). The cohort was followed up after 30 years and data from the Swedish Cause of Death Registry and the Swedish Cancer Registry were extracted. Hazard ratios (HRs) were calculated using Cox regression models. RESULT: High DHT levels were positively correlated to a lower risk for prostate cancer death in the entire cohort: HR = 0.44 (0.25-0.77 95% confidence interval [CI]). The positive correlation remained significant for the subgroup analysis. HR for the men enrolled in the study without any clinical signs of prostate cancer was 0.25 (0.07-0.88 95% CI) and for the men with a prostate cancer diagnosis at time of inclusion: HR = 0.50 (0.26-0.94 95% CI). CONCLUSION: DHT is negatively associated with long-term prostate cancer death regardless of clinical presentation at time of inclusion.

Enhanced Electrode Deposition for On-Chip Integrated Micro-Supercapacitors by Controlled Surface Roughening.

On-chip micro-supercapacitors (MSCs), integrated with energy harvesters, hold substantial promise for developing self-powered wireless sensor systems. However, MSCs have conventionally been manufactured through techniques incompatible with semiconductor fabrication technology, the most significant bottleneck being the electrode deposition technique. Utilization of spin-coating for electrode deposition has shown potential to deliver several complementary metal-oxide-semiconductor (CMOS)-compatible MSCs on a silicon substrate. Yet, their limited electrochemical performance and yield over the substrate have remained challenges obstructing their subsequent integration. We report a facile surface roughening technique for improving the wafer yield and the electrochemical performance of CMOS-compatible MSCs, specifically for reduced graphene oxide as an electrode material. A 4 nm iron layer is deposited and annealed on the wafer substrate to increase the roughness of the surface. In comparison to standard nonroughened MSCs, the increase in surface roughness leads to a 78% increased electrode thickness, 21% improvement in mass retention, 57% improvement in the uniformity of the spin-coated electrodes, and a high yield of 87% working devices on a 2″ silicon substrate. Furthermore, these improvements directly translate to higher capacitive performance with enhanced rate capability, energy, and power density. This technique brings us one step closer to fully integrable CMOS-compatible MSCs in self-powered systems for on-chip wireless sensor electronics.

Impact of electrode geometry and thickness on planar on-chip microsupercapacitors.

We report an assessment of the influence of both finger geometry and vertically-oriented carbon nanofiber lengths in planar micro-supercapacitors. Increasing the finger number leads to an up-scaling in areal power densities, which increases with scan rate. Growing the nanofibers longer, however, does not lead to a proportional growth in capacitance, proposedly related to limited ion penetration of the electrode.

Maintaining Transparency of a Heated MEMS Membrane for Enabling Long-Term Optical Measurements on Soot-Containing Exhaust Gas.

Ensuring optical transparency over a wide spectral range of a window with a view into the tailpipe of the combustion engine, while it is exposed to the harsh environment of soot-containing exhaust gas, is an essential pre-requisite for introducing optical techniques for long-term monitoring of automotive emissions. Therefore, a regenerable window composed of an optically transparent polysilicon-carbide membrane with a diameter ranging from 100 µm up to 2000 µm has been fabricated in microelectromechanical systems (MEMS) technology. In the first operating mode, window transparency is periodically restored by pulsed heating of the membrane using an integrated resistor for heating to temperatures that result in oxidation of deposited soot (600-700 °C). In the second mode, the membrane is kept transparent by repelling soot particles using thermophoresis. The same integrated resistor is used to yield a temperature gradient by continuous moderate-temperature heating. Realized devices have been subjected to laboratory soot exposure experiments. Membrane temperatures exceeding 500 °C have been achieved without damage to the membrane. Moreover, heating of membranes to ΔT = 40 °C above gas temperature provides sufficient thermophoretic repulsion to prevent particle deposition and maintain transparency at high soot exposure, while non-heated identical membranes on the same die and at the same exposure are heavily contaminated.

Carbon-Based Electrode Materials for Microsupercapacitors in Self-Powering Sensor Networks: Present and Future Development.

There is an urgent need to fulfill future energy demands for micro and nanoelectronics. This work outlines a number of important design features for carbon-based microsupercapacitors, which enhance both their performance and integration potential and are critical for complimentary metal oxide semiconductor (CMOS) compatibility. Based on these design features, we present CMOS-compatible, graphene-based microsupercapacitors that can be integrated at the back end of the line of the integrated circuit fabrication. Electrode materials and their interfaces play a crucial role for the device characteristics. As such, different carbon-based materials are discussed and the importance of careful design of current collector/electrode interfaces is emphasized. Electrode adhesion is an important factor to improve device performance and uniformity. Additionally, doping of the electrodes can greatly improve the energy density of the devices. As microsupercapacitors are engineered for targeted applications, device scaling is critically important, and we present the first steps toward general scaling trends. Last, we outline a potential future integration scheme for a complete microsystem on a chip, containing sensors, logic, power generation, power management, and power storage. Such a system would be self-powering.

A Micromachined Coupled-Cantilever for Piezoelectric Energy Harvesters.

This paper presents a demonstration of the feasibility of fabricating micro-cantilever harvesters with extended stress distribution and enhanced bandwidth by exploiting an M-shaped two-degrees-of-freedom design. The measured mechanical response of the fabricated device displays the predicted dual resonance peak behavior with the fundamental peak at the intended frequency. This design has the features of high energy conversion efficiency in a miniaturized environment where the available vibrational energy varies in frequency. It makes such a design suitable for future large volume production of integrated self powered sensors nodes for the Internet-of-Things.

Long-Term Outcome of a Single Intervention Population Based Prostate Cancer Screening Study.

PURPOSE: We evaluated the long-term effect of screening for prostate cancer. MATERIALS AND METHODS: In 1988 we randomly selected 2,400 men from a background population of 27,464 men. The 2,400 men were invited to undergo screening, of whom 1,779 (74%) accepted and were examined with digital rectal examination, ultrasound and prostate specific antigen measurement. Biopsy was performed if there were suspicious findings on ultrasound or digital rectal examination, or prostate specific antigen was greater than 10 ng/ml. The subpopulations have now been reassessed after 20 years. RESULTS: Participants had a decreased overall mortality rate compared to the source population (IRR 0.93, 95% CI 0.86-0.98). Nonparticipants had an increased overall mortality rate (IRR 1.25, 95% CI 1.14-1.37). There was no difference between the groups in prostate cancer specific survival. The incidence of prostate cancer remained higher in the screened population throughout followup. CONCLUSIONS: A single screening intervention in men 50 to 75 years old using prostate specific antigen, digital rectal examination and transrectal ultrasound, and a prostate specific antigen cutoff of 10 ng/ml for biopsy carried a significant risk of prostate cancer detection without a concomitant reduction in prostate cancer specific mortality after 20 years. This intervention should not be considered for public screening. Nonparticipants were at greater risk for death of all causes. In addition to being a single intervention trial, the limitations of this study include an outdated prostate specific antigen cutoff for biopsy. Despite the outdated screening method the source population failed to reach the same level of prostate cancer incidence as the screened population even after 20 years.

Cobalt (II) chloride promoted formation of honeycomb patterned cellulose acetate films.

CoCl(2) containing honeycomb patterned films were prepared from cellulose acetate (CA)/CoCl(2)/acetone solutions by the breath figure method in a wide range of humidities. Size and pore regularity depend on the CA/CoCl(2) molar ratio and humidity. When replacing CoCl(2) with Co(NO(3))(2) or CoBr(2), no formation of ordered porosity in the cellulose acetate films is observed. According to data from scanning electron microscopy (SEM), Energy Dispersive X-ray Microanalysis (EDX), X-ray Diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy, the key role in the formation of honeycomb structures can be attributed to the physical and chemical properties of CoCl(2) - hygroscopicity, low interaction with CA, and extraction from CA/CoCl(2)/acetone solution by water droplets condensed on the surface of the CA/CoCl(2) solution. Obtained films are prospective for using in catalysis, hydrogen fuel cells, and optical sensing materials.

Changes in tooth mortality between 1990 and 2002 among adults in Västerbotten County, Sweden: influence of socioeconomic factors, general health, smoking, and dental care habits on tooth mortality.

The objectives of the study were to analyse changes in tooth mortality among adults in Västerbotten County, Sweden, between 1990 and 2002 and determine whether socioeconomic factors, general health, smoking, and dental care habits influenced tooth mortality. The study was based on samples drawn from the adult population in Västerbotten County in 1990 and 2002. The studied age groups were 35-, 50-, and 65-year-olds. In 2002 75-year-olds were included. The surveys comprised a clinical examination and a questionnaire.The latter focused on oro-facial symptoms, socioeconomic factors, general health, smoking, and dental care habits. Complete data were obtained from 715 individuals in 1990 and from 768 individuals in 2002.Variables used to depict tooth mortality were edentulousness, occlusal supporting zones (Eichner index), and number of teeth. The prevalence of edentulousness in Västerbotten County decreased from 12.7% in 1990 to 3.7% in 2002 (P < 0.001). The mean number of teeth increased in all age groups between 1990 and 2002, and so did the number of individuals with tooth contact in all occlusal supporting zones and no gaps between teeth. Low educational level, weak economic status, smoking, and irregular visits to the dental clinic were all significantly related to increased tooth mortality. Between 1990 and 2002 tooth mortality decreased significantly in the adult population of Västerbotten County, Sweden. Cross-sectional analysis identified socioeconomic factors, smoking, and irregular use of dental care services as being related to tooth mortality in both 1990 and 2002.

Allopregnanolone has no effect on startle response and prepulse inhibition of startle response in patients with premenstrual dysphoric disorder or healthy controls.

BACKGROUND: Allopregnanolone is an endogenous neuroactive steroid which, through the binding to the GABA(A) receptor, enhances inhibitory neurotransmission and exerts anxiolytic, sedative and antiepileptic effects. Following acute administration, allopregnanolone reliably acts as an anxiolytic compound. The primary aim of this study was to investigate if allopregnanolone, administered to healthy women and women with premenstrual dysphoric disorder (PMDD), would have an anxiolytic effect, expressed as a decreased startle response. MATERIALS AND METHODS: Sixteen PMDD patients and twelve healthy controls completed the study. The participants were scheduled for the startle tests twice in the luteal phase. During the test sessions an intravenous allopregnanolone and placebo bolus injection was administered in double-blinded, randomized order at intervals of 48 h. Following the allopregnanolone/placebo injections startle response and prepulse inhibition of startle response (PPI) were assessed by electromyography. RESULTS: Following the intravenous allopregnanolone administration the serum concentrations of allopregnanolone increased to 50-70 nmol/l, corresponding to levels that are seen during pregnancy. The obtained serum concentrations of allopregnanolone were significantly lower in PMDD patients than among the healthy controls, p<0.05. The allopregnanolone injection resulted in significant increases of self-rated sedation in both groups, p<0.01. Allopregnanolone did not induce any changes in startle response or prepulse inhibition of startle response in comparison to placebo. No differences in allopregnanolone-induced changes in startle response or PPI could be detected between PMDD patients and controls subjects. CONCLUSION: Startle response and PPI were unaffected by acute intravenous administration of allopregnanolone in PMDD patients and healthy controls.

The effect of the neuroactive steroid 5beta-pregnane-3beta, 20(R)-diol on the time course of GABA evoked currents is different to that of pregnenolone sulphate.

The endogenous progesterone metabolite allopregnanolone has a number of properties including anesthetic, sedative, antiepileptic, anxiolytic, impaired memory function and negative mood symptoms. Allopregnanolone is a potent positive GABA(A) receptor function modulators. In contrast, 3beta-hydroxy-steroids (3beta-steroids) usually modulate the GABA(A) receptor negatively. They have attracted some interest for their possible use as therapeutic agents that could counteract the negative symptoms induced by allopregnanolone. Two hypotheses for the action of 3beta-steroids have been proposed: 1) 3beta-steroids act in a similar way to pregnenolone sulphate, which non-competitively reduces GABA(A) receptor activity. 2) 3beta-steroids specifically antagonize the effect of allopregnanolone. We have therefore tried to clarify this issue by comparing the effect of pregnenolone sulphate and 5beta-pregnane-3beta, 20(R)-diol on the GABA-evoked currents by the patch clamp technique on neurons from the medial preoptic nucleus. Both pregnenolone sulphate and 5beta-pregnane-3beta, 20(R)-diol increase the desensitization rate of the current response evoked by a 2 s GABA application. However, their effects on other parameters of the GABA evoked currents differed in degree and sometimes even in direction. The actions of pregnenolone sulphate and 5beta-pregnane-3beta, 20(R)-diol were not altered in the presence of allopregnanolone, which indicates that they do not directly interact with allopregnanolone. In addition, when 5beta-pregnane-3beta, 20(R)-diol was tested on spontaneous inhibitory postsynaptic currents (sIPSCs), it dramatically reduced the allopregnanolone-induced prolongation of the decay time constant but it had no effect on the decay under control conditions. In conclusion, the effect of 5beta-pregnane-3beta, 20(R)-diol on GABA-evoked currents is different to that of pregnenolone sulphate in medial preoptic nucleus neurons.

Compatibility assessment of CVD growth of carbon nanofibers on bulk CMOS devices.

We compare the level of deterioration in the basic functionality of individual transistors on ASIC chips fabricated in standard 130 nm bulk CMOS technology when subjected to three disparate CVD techniques with relatively low processing temperature to grow carbon nanostructures. We report that the growth technique with the lowest temperature has the least impact on the transistor behavior.