Effects of the Flying Start on Estimated Short Sprint Profiles Using Timing Gates.

Short sprints are predominantly assessed using timing gates and analyzed through parameters of the mono-exponential equation, including estimated maximal sprinting speed (MSS) and relative acceleration (TAU), derived maximum acceleration (MAC), and relative propulsive maximal power (PMAX), further referred to as the No Correction model. However, the frequently recommended flying start technique introduces a bias during parameter estimation. To correct this, two additional models (Estimated TC and Estimated FD) were proposed. To estimate model precision and sensitivity to detect the change, 31 basketball players executed multiple 30 m sprints. Athlete performance was simultaneously measured by a laser gun and timing gates positioned at 5, 10, 20, and 30 m. Short sprint parameters were estimated using a laser gun, representing the criterion measure, and five different timing gate models, representing the practical measures. Only the MSS parameter demonstrated a high agreement between the laser gun and timing gate models, using the percent mean absolute difference (%MAD) estimator (%MAD < 10%). The MSS parameter also showed the highest sensitivity, using the minimum detectable change estimator (%MDC95), with an estimated %MDC95 < 17%. Interestingly, sensitivity was the highest for the No Correction model (%MDC95 < 7%). All other parameters and models demonstrated an unsatisfying level of sensitivity. Thus, sports practitioners should be cautious when using timing gates to estimate maximum acceleration indices and changes in their respective levels.

Peptide Toxins from Antarctica: The Nemertean Predator and Scavenger Parborlasia corrugatus (McIntosh, 1876).

Peptide toxins from marine invertebrates have found use as drugs and in biotechnological applications. Many marine habitats, however, remain underexplored for natural products, and the Southern Ocean is among them. Here, we report toxins from one of the top predators in Antarctic waters: the nemertean worm Parborlasia corrugatus (McIntosh, 1876). Transcriptome mining revealed a total of ten putative toxins with a cysteine pattern similar to that of alpha nemertides, four nemertide-beta-type sequences, and two novel full-length parborlysins. Nemertean worms express toxins in the epidermal mucus. Here, the expression was determined by liquid chromatography combined with mass spectrometry. The findings include a new type of nemertide, 8750 Da, containing eight cysteines. In addition, we report the presence of six cysteine-containing peptides. The toxicity of tissue extracts and mucus fractions was tested in an Artemia assay. Notably, significant activity was observed both in tissue and the high-molecular-weight mucus fraction, as well as in a parborlysin fraction. Membrane permeabilization experiments display the membranolytic activity of some peptides, most prominently the parborlysin fraction, with an estimated EC50 of 70 nM.

Speed Matters in Nordic Hamstring Exercise: Higher Peak Knee Flexor Force during Fast Stretch-Shortening Variant Compared to Standard Slow Eccentric Execution in Elite Athletes.

Hamstring strain injuries are prevalent in many sports. Research has demonstrated that the Nordic hamstring exercise (NHE), a knee-dominant exercise addressing the posterior chain muscles, can aid in reducing the risk of hamstring injuries in athletes. However, most research on hamstring injury prevention has focused on performing the eccentric version of the NHE (NHEECC). In contrast, in sports, it is quite frequent for athletes to use an eccentric-concentric version of the NHE. Additionally, eccentric NHE is typically performed using a slow, controlled tempo. The effect of a fast stretch-shortening cycle NHE (NHESSC) compared to standard slow NHEECC on peak knee flexor force has not been investigated. The aim of the study was therefore to investigate fast NHESSC vs. standard slow NHEECC. Our hypothesis posited that peak knee flexor force would be greater for fast NHESSC compared with standard slow NHEECC. The study involved 22 elite athletes (actively competing in both national and international events) consisting of female (n = 10) and male (n = 7) track and field athletes and male football players (n = 5), aged 17-31 years. The participants performed maximum trials of slow NHEECC and fast NHESSC repetitions in which measurement of bilateral peak knee flexor force was conducted at the ankle with the use of a load cell. During the NHEs, a linear encoder was used to measure both the position where the peak knee flexor force was recorded and the average eccentric velocity. SSC contributed to an enhanced NHE performance, where bilateral absolute peak knee flexor force was 13% higher for fast NHESSC vs. standard slow NHEECC (822 vs. 726 N, p < 0.01, ES = 0.54). Participants achieved a 32% greater forward distance at the breakpoint stage during NHEECC compared to the coupling phase for NHESSC (54 vs. 41 cm, p < 0.001, ES = 1.37). Eccentric average velocity was more than three times higher for NHESSC compared with NHEECC (0.38 vs. 0.12 m/s, p < 0.001, ES = 3.25). The key findings of this study were that SSC contributed to an enhanced NHE performance, where absolute peak knee flexor force was 13% greater for fast NHESSC compared to standard slow NHEECC. The fast NHESSC could therefore be an interesting alternative to the standard slow NHEECC execution, as it may offer potential advantages for sprint performance, as well as hamstring injury prevention and rehabilitation.

Sprint skating profile of competitive male bandy players: determination of positional differences and playing level.

This study aimed to compare sprint skating profile characteristics of the different playing positions of junior and senior bandy players. In total, 111 male national-level bandy players (age: 20.7 ± 5.0 years, height: 1.80 ± 0.05 m, body mass: 76.4 ± 0.4 kg, training experience: 13.8 ± 5.0 yrs) were tested on their sprint skating profile over 80 m. The main findings were that no differences between positions were found in sprint skating performance (speed and acceleration), but that elite players were in general heavier (p < 0.05) than junior players (80.0 ± 7.1 vs. 73.1 ± 8.1 kg), they could accelerate faster (2.96 ± 0.22 vs. 2.81 ± 0.28 m/s2), and they reached a higher velocity (10.83 ± 0.37 vs. 10.24 ± 0.42 m/s) earlier over 80 m than the junior players. This implies that junior level players should spend more time in power and sprint training to meet the specific demands of playing at a higher, elite level.

Differences in Peak Knee Flexor Force between Eccentric-Only and Combined Eccentric-Concentric Nordic Hamstring Exercise.

In many sports, the hamstring strain injury is a common injury. There is evidence that the Nordic hamstring exercise (NHE), a knee flexor exercise, can reduce hamstring injury risk in athletes. In research on hamstring injury prevention, eccentric-only NHE is typically performed, whereas in sports, it is relatively common for athletes to perform NHE eccentrically-concentrically. Further, NHE strength is generally assessed by measuring knee flexor force through an ankle brace, attached atop of a load cell. An alternative method might be to assess knee flexor force about the knee joint using a force plate. The aim of the study was to investigate differences in peak knee flexor force between eccentric-only and combined eccentric-concentric NHE. The purpose was also to determine the correlation between hamstring force measured at the ankle using a load cell (current gold standard) and force assessed about the knee joint using a force plate during NHE. Fifteen junior and senior elite soccer and track and field athletes (3 women and 12 men aged 17-27 years) performed eccentric NHE (ENHE) in which they leaned forward as far as possible until breakpoint and eccentric-concentric NHE (ECNHE) where they returned to the starting position. A linear encoder measured the position at which peak force occurred during the NHEs. Force assessed at the ankle differed significantly (678 vs. 600 N, p < 0.05), whereas force about the knee joint did not (640 vs. 607 N, p > 0.05) between ENHE and ECNHE (12 and 5% difference, respectively). The forward distance achieved by the participants in cm at breakpoint for ENHE was 37% higher than at the coupling phase for ECNHE (74 vs. 54 cm, p < 0.001). Very strong significant (p < 0.01) correlations were noted between peak force assessed at the ankle and about the knee joint for ENHE and ECNHE, r = 0.96 and r = 0.99, respectively. Our results suggest that ECNHE, where peak knee flexor force was reached with 37% less forward movement, may complement ENHE, i.e., during hamstring injury rehabilitation, where a position of great knee extension may not be well tolerated by the athlete. Further, assessing knee flexor force about the knee joint using a force plate may provide an alternative to measuring force at the ankle using a load cell when testing NHE strength.

Mechanisms of Hamstring Injury in Professional Soccer Players: Video Analysis and Magnetic Resonance Imaging Findings.

OBJECTIVE: To describe the injury mechanisms and magnetic resonance imaging (MRI) findings in acute hamstring injuries of male soccer players using a systematic video analysis. DESIGN: Descriptive case series study of consecutive acute hamstring injuries from September 2017 to January 2022. SETTING: Two specialized sports medicine hospitals. PARTICIPANTS: Professional male soccer players aged between 18 and 40 years, referred for injury assessment within 7 days after an acute hamstring injury, with an available video footage of the injury and positive finding on MRI. INDEPENDENT VARIABLES: Hamstring injury mechanisms (specific scoring based on standardized models) in relation to hamstring muscle injury MRI findings. MAIN OUTCOME MEASURES: Hamstring injury mechanism (playing situation, player/opponent behavior, movement, and biomechanical body positions) and MRI injury location. RESULTS: Fourteen videos of acute hamstring injuries in 13 professional male soccer players were analyzed. Three different injury mechanisms were seen: mixed-type (both sprint-related and stretch-related, 43%), stretch-type (36%), and sprint-type (21%). Most common actions during injury moments were change of direction (29%), kicking (29%), and running (21%). Most injuries occurred at high or very high horizontal speed (71%) and affected isolated proximal biceps femoris (BF) (36%). Most frequent body positions at defined injury moments were neutral trunk (43%), hip flexion 45-90 degrees (57%), and knee flexion <45 degrees (93%). Magnetic resonance imaging findings showed that 79% were isolated single-tendon injuries. CONCLUSIONS: According to a video analysis, most hamstring injuries in soccer occur during high-speed movements. Physicians should suspect proximal and isolated single-tendon-most often BF-hamstring injury, if represented injury mechanisms are seen during game play. In addition to sprinting and stretching, also mixed-type injury mechanisms occur.

Sprint skating profile of competitive female bandy players: An analysis of positional and playing-level differences.

There is no research examining female bandy players, which creates a gap of knowledge of female skating performance and its determinants with male skating performance, not only in bandy but also in exercise science in general. Therefore, the aim of this explorative study was to investigate position and playing-level differences in the sprint skating performance and anthropometrics of 74 elite female bandy players (age: 18.9 ± 4.1 years; height: 1.67 ± 0.06 m; body mass: 63.2 ± 7.4 kg). Participants were categorised according to playing level (26 elite and 48 junior elite players) and position (22 defenders, 35 midfielders, and 17 forwards). They were tested on their anthropometric characteristics and sprint linear skating profile over 80 m with the split times measured at 10, 20, 40, 50, 60, 70, and 80 m to calculate the average velocities between these different 10 m intervals. Results revealed that elite players had more training experience, were heavier, could accelerate faster, and reached a higher maximal velocity than the junior elite players (9.52 ± 0.37 vs 8.84 ± 0.40 m/s, respectively). In general, defenders were heavier than forwards, and the elite forwards accelerated faster in the first 10 m than the midfielders (p = 0.041). In summary, playing level and position, body mass, and training experience modulated skating sprint performance. The findings suggest that female junior-level players should spend more time developing skating sprint and acceleration abilities to meet the specific demands of playing at the elite level. Moreover, the coaches and professionals who work with female bandy players should be aware that the development of acceleration ability is more important for forwards.

Functional Characterization of the Nemertide α Family of Peptide Toxins.

Peptide toxins find use in medicine, biotechnology, and agriculture. They are exploited as pharmaceutical tools, particularly for the investigation of ion channels. Here, we report the synthesis and activity of a novel family of peptide toxins: the cystine-knotted α nemertides. Following the prototypic α-1 and -2 (1 and 2), six more nemertides were discovered by mining of available nemertean transcriptomes. Here, we describe their synthesis using solid phase peptide chemistry and their oxidative folding by using an improved protocol. Nemertides α-2 to α-7 (2-7) were produced to characterize their effect on voltage-gated sodium channels (Blatella germanica BgNaV1 and mammalian NaVs1.1-1.8). In addition, ion channel activities were matched to in vivo tests using an Artemia microwell assay. Although nemertides demonstrate high sequence similarity, they display variability in activity on the tested NaVs. The nemertides are all highly toxic to Artemia, with EC50 values in the sub-low micromolar range, and all manifest preference for the insect BgNaV1 channel. Structure-activity relationship analysis revealed key residues for NaV-subtype selectivity. Combined with low EC50 values (e.g., NaV1.1: 7.9 nM (α-6); NaV1.3: 9.4 nM (α-5); NaV1.4: 14.6 nM (α-4)) this underscores the potential utility of α-nemertides for rational optimization to improve selectivity.

Solution NMR and racemic crystallography provide insights into a novel structural class of cyclic plant peptides.

Head-to-tail cyclic and disulfide-rich peptides are natural products with applications in drug design. Among these are the PawS-Derived Peptides (PDPs) produced in seeds of the daisy plant family. PDP-23 is a unique member of this class in that it is twice the typical size and adopts two ß-hairpins separated by a hinge region. The ß-hairpins, both stabilised by a single disulfide bond, fold together into a V-shaped tertiary structure creating a hydrophobic core. In water two PDP-23 molecules merge their hydrophobic cores to form a square prism quaternary structure. Here, we synthesised PDP-23 and its enantiomer comprising d-amino acids and achiral glycine, which allowed us to confirm these solution NMR structural data by racemic crystallography. Furthermore, we discovered the related PDP-24. NMR analysis showed that PDP-24 does not form a dimeric structure and it has poor water solubility, but in less polar solvents adopts near identical secondary and tertiary structure to PDP-23. The natural role of these peptides in plants remains enigmatic, as we did not observe any antimicrobial or insecticidal activity. However, the plasticity of these larger PDPs and their ability to change structure under different conditions make them appealing peptide drug scaffolds.

Functionality of primary hepatic non-parenchymal cells in a 3D spheroid model and contribution to acetaminophen hepatotoxicity.

In addition to hepatocytes, the liver comprises a host of specialised non-parenchymal cells which are important to consider in the development of in vitro models which are both physiologically and toxicologically relevant. We have characterized a 3D co-culture system comprising primary human hepatocytes (PHH) and non-parenchymal cells (NPC) and applied it to the investigation of acetaminophen-induced toxicity. Firstly, we titrated ratios of PHH:NPC and confirmed the presence of functional NPCs via both immunohistochemistry and activation with both LPS and TGF-ß. Based on these data we selected a ratio of 2:1 PHH:NPC for further studies. We observed that spheroids supplemented with NPCs were protected against acetaminophen (APAP) toxicity as determined by ATP (up to threefold difference in EC50 at day 14 compared to hepatocytes alone) and glutathione depletion, as well as miR-122 release. APAP metabolism was also altered in the presence of NPCs, with significantly lower levels of APAP-GSH detected. Expression of several CYP450 enzymes involved in the bioactivation of APAP was also lower in NPC-containing spheroids. Spheroids containing NPCs also expressed higher levels of miRNAs which have been implicated in APAP-induced hepatotoxicity, including miR-382 and miR-155 which have potential roles in liver regeneration and inflammation, respectively. These data indicate that the interaction between hepatocytes and NPCs can have significant metabolic and toxicological consequences important for the correct elucidation of hepatic safety mechanisms.

From carbohydrates to fat: Trends in food intake among Swedish nutrition students from 2002 to 2017.

Earlier studies have implied a change in dietary habits of the Swedish population towards a low carbohydrate, high fat diet. Questions have been raised about the development in recent years and potential health effects. We have investigated the dietary intake of Swedish female students enrolled in a university nutrition course between 2002 and 2017. The students carried out self-reporting of all food and drink intake over one weekday and one weekend day. Intake of macronutrients (E%) and micronutrients were calculated for the whole period while statistical analysis was performed for changes between 2009 and 2017 (729 women). Results showed significant changes in carbohydrate intake (from 47.0 to 41.4 E%) and fat intake (from 31.7 to 37.5 E%). Carbohydrate intake was significantly lower than the Nordic Nutrition Recommendations (45-60 E%). However, daily fiber intake remains high (3.0 g/MJ) in a national context, and intake of vitamin D and folate appears to increase during the period. The results suggest that the observed national transition from carbohydrate to fat intake persists, and that it might be especially evident among individuals interested in food and nutrition. Considering the fiber and micronutrient intake, the change is not necessarily unfavorable for this particular group.

Synthesis of di-docosahexaenoyl (C22:6)-bis(monoacylglycerol) phosphate in unlabelled and C-13 labelled forms for use as a biomarker of drug induced phospholipidosis.

Di-docosahexaenoyl (C22:6)-bis(monoacylglycerol) phosphate (BMP) has been identified as a promising biomarker for drug-induced phospholipidosis (DIPL). Both unlabelled and stable isotope labelled versions of BMP were desired for use as internal standards. Isopropylideneglycerol was converted to 4-methoxyphenyldiphenylmethyl-3-PMB-glycerol in three steps. Initially, the 2-postion of the glycerol was protected as a t-butyldiphenylsilyl ether, which proved to be a mistake; deprotection of the ether resulted in the decomposition of the compound. A switch to a t-butyldimethylsilyl ether protecting group resulted in an intermediate that could be deprotected to the alcohol to give the target compound after salt exchange. The same procedure was used to prepare [13 C6 ]BMP from [13 C3 ]glycerol.

The Toxins of Nemertean Worms.

Most ribbon worms (phylum: Nemertea) are found in marine environments, where they act as predators and scavengers. They are characterized by an eversible proboscis that isused to hunt for prey and thick mucus covering their skin. Both proboscis and epidermal mucus mediate toxicity to predators and preys. Research into the chemical nature of the substances that render toxicity has not been extensive, but it has nevertheless led to the identification of several compounds of potential medicinal use or for application in biotechnology. This review provides a complete account of the current status of research into nemertean toxins.

Intraperitoneal α-Emitting Radioimmunotherapy with 211At in Relapsed Ovarian Cancer: Long-Term Follow-up with Individual Absorbed Dose Estimations.

Eliminating microscopic residual disease with α-particle radiation is theoretically appealing. After extensive preclinical work with α-particle-emitting 211At, we performed a phase I trial with intraperitoneal α-particle therapy in epithelial ovarian cancer using 211At conjugated to MX35, the antigen-binding fragments-F(ab')2-of a mouse monoclonal antibody. We now present clinical outcome data and toxicity in a long-term follow-up with individual absorbed dose estimations. Methods: Twelve patients with relapsed epithelial ovarian cancer, achieving a second complete or nearly complete response with chemotherapy, received intraperitoneal treatment with escalating (20-215 MBq/L) activity concentrations of 211At-MX35 F(ab')2.Results: The activity concentration was escalated to 215 MBq/L without any dose-limiting toxicities. Most toxicities were low-grade and likely related to the treatment procedure, not clearly linked to the α-particle irradiation, with no observed hematologic toxicity. One grade 3 fatigue and 1 grade 4 intestinal perforation during catheter implantation were observed. Four patients had a survival of more than 6 y, one of whom did not relapse. At progression, chemotherapy was given without signs of reduced tolerability. Overall median survival was 35 mo, with a 1-, 2-, 5-, and 10-y survival of 100%, 83%, 50%, and 25%, respectively. Calculations of the absorbed doses showed that a lower specific activity is associated with a lower single-cell dose, whereas a high specific activity may result in a lower central dose in microtumors. Individual differences in absorbed dose to possible microtumors were due to variations in administered activity and the specific activity. Conclusion: No apparent signs of radiation-induced toxicity or decreased tolerance to relapse therapy were observed. The dosimetric calculations show that further optimization is advisable to increase the efficacy and reduce possible long-term toxicity.

Peptide ion channel toxins from the bootlace worm, the longest animal on Earth.

Polypeptides from animal venoms have found important uses as drugs, pharmacological tools, and within biotechnological and agricultural applications. We here report a novel family of cystine knot peptides from nemertean worms, with potent activity on voltage-gated sodium channels. These toxins, named the α-nemertides, were discovered in the epidermal mucus of Lineus longissimus, the 'bootlace worm' known as the longest animal on earth. The most abundant peptide, the 31-residue long α-1, was isolated, synthesized, and its 3D NMR structure determined. Transcriptome analysis including 17 species revealed eight α-nemertides, mainly distributed in the genus Lineus. α-1 caused paralysis and death in green crabs (Carcinus maenas) at 1 µg/kg (~300 pmol/kg). It showed profound effect on invertebrate voltage-gated sodium channels (e.g. Blattella germanica Nav1) at low nanomolar concentrations. Strong selectivity for insect over human sodium channels indicates that α-nemertides can be promising candidates for development of bioinsecticidal agents.

Naloxegol, an opioid antagonist with reduced CNS penetration: Mode-of-action and human relevance for rat testicular tumours.

Naloxegol is an opioid antagonist which has been developed for the treatment of patients with opioid induced constipation. In the nonclinical safety program naloxegol was shown to have a very benign toxicity profile. In the rat, but not the mouse, 2-year carcinogenicity study a change in tumour pattern with an increase in testicular Leydig cell tumours (LCT) was observed after dosing at high (supra-pharmacological) concentrations. To establish the basis of the increase in LCT and to assess its potential relevance to humans, studies to exclude and potentially identify mode-of-action (MoA) were performed. A genotoxic mechanism was ruled out following negative results in the Ames, mouse lymphoma, and micronucleus assays. An effect on androgen metabolism was excluded since the treatment of rats with naloxegol for 14days did not result in any induction of CYP protein levels. It was demonstrated that administration of centrally restricted opioid antagonists naloxegol or methylnaltrexone at high doses induced an increase in LH release with no clear increase in testosterone, in contrast to the centrally acting opioid antagonist naloxone, which showed marked increases in both LH and testosterone. LCT due to increased LH stimulation is common in rats but not documented in humans. Collectively, the lack of genotoxicity signal, the lack of androgen effect, the increase in LH secretion in rats, which is no considered to be relevant for LCT formation in humans, and high margins to clinical exposures, the observed increase in LCT in the rat is not expected to be clinically relevant.

The Bacterial (Vibrio alginolyticus) Production of Tetrodotoxin in the Ribbon Worm Lineus longissimus-Just a False Positive?

We test previous claims that the bacteria Vibrio alginolyticus produces tetrodotoxin (TTX) when living in symbiosis with the nemertean Lineus longissimus by a setup with bacteria cultivation for TTX production. Toxicity experiments on the shore crab, Carcinus maenas, demonstrated the presence of a paralytic toxin, but evidence from LC-MS and electrophysiological measurements of voltage-gated sodium channel-dependent nerve conductance in male Wistar rat tissue showed conclusively that this effect did not originate from TTX. However, a compound of similar molecular weight was found, albeit apparently non-toxic, and with different LC retention time and MS/MS fragmentation pattern than those of TTX. We conclude that C. maenas paralysis and death likely emanate from a compound <5 kDa, and via a different mechanism of action than that of TTX. The similarity in mass between TTX and the Vibrio-produced low-molecular-weight, non-toxic compound invokes that thorough analysis is required when assessing TTX production. Based on our findings, we suggest that re-examination of some published claims of TTX production may be warranted.

Diet inequality prevails among consumers interested and knowledgeable in nutrition.

BACKGROUND: Previous studies have demonstrated a correlation between diet cost and adherence to nutritional recommendations among consumers in general. This has adverse effects on diet and health inequality. It could be hypothesized that consumers knowledgeable in nutrition escape this correlation. OBJECTIVE: Investigate whether the previously observed relationship between diet cost and nutritional quality prevails among consumers with an above-average interest in and knowledge of nutrition. DESIGN: Full open diet registrations of 330 students taking a basic university-level course in nutrition over a total of 780 days. RESULTS: The consumers with the highest daily average diet cost differ from the lowest cost quartile: The diets had higher micronutrient density, more fruits and vegetables, and lower energy density. The highest cost daily diet quartile had a significantly higher energy adjusted intake of the micronutrients that were on average consumed below the recommendation (vitamin D, folate, and iron for women). On the other hand, alcohol intake was significantly higher among the high diet cost group. The highest diet cost respondents consumed more fish, meat, coffee, and spreads, whereas the lowest diet cost respondents had a higher consumption of cereals, bread, jam, sausage, and milk. CONCLUSIONS: Dietary differences prevail even in the above-average interested and knowledgeable group. The respondents did not use their higher level of knowledge to break this commonly observed relationship. This suggests that an increased minimum level of knowledge in nutrition may not by itself eliminate dietary inequality.

Absorbed Doses and Risk Estimates of (211)At-MX35 F(ab')2 in Intraperitoneal Therapy of Ovarian Cancer Patients.

PURPOSE: Ovarian cancer is often diagnosed at an advanced stage with dissemination in the peritoneal cavity. Most patients achieve clinical remission after surgery and chemotherapy, but approximately 70% eventually experience recurrence, usually in the peritoneal cavity. To prevent recurrence, intraperitoneal (i.p.) targeted α therapy has been proposed as an adjuvant treatment for minimal residual disease after successful primary treatment. In the present study, we calculated absorbed and relative biological effect (RBE)-weighted (equivalent) doses in relevant normal tissues and estimated the effective dose associated with i.p. administration of (211)At-MX35 F(ab')2. METHODS AND MATERIALS: Patients in clinical remission after salvage chemotherapy for peritoneal recurrence of ovarian cancer underwent i.p. infusion of (211)At-MX35 F(ab')2. Potassium perchlorate was given to block unwanted accumulation of (211)At in thyroid and other NIS-containing tissues. Mean absorbed doses to normal tissues were calculated from clinical data, including blood and i.p. fluid samples, urine, γ-camera images, and single-photon emission computed tomography/computed tomography images. Extrapolation of preclinical biodistribution data combined with clinical blood activity data allowed us to estimate absorbed doses in additional tissues. The equivalent dose was calculated using an RBE of 5 and the effective dose using the recommended weight factor of 20. All doses were normalized to the initial activity concentration of the infused therapy solution. RESULTS: The urinary bladder, thyroid, and kidneys (1.9, 1.8, and 1.7 mGy per MBq/L) received the 3 highest estimated absorbed doses. When the tissue-weighting factors were applied, the largest contributors to the effective dose were the lungs, stomach, and urinary bladder. Using 100 MBq/L, organ equivalent doses were less than 10% of the estimated tolerance dose. CONCLUSION: Intraperitoneal (211)At-MX35 F(ab')2 treatment is potentially a well-tolerated therapy for locally confined microscopic ovarian cancer. Absorbed doses to normal organs are low, but because the effective dose potentially corresponds to a risk of treatment-induced carcinogenesis, optimization may still be valuable.

Dropout revisited: patient- and therapist-initiated discontinuation of psychotherapy as a function of organizational instability.

OBJECTIVE: To explore the association between the stability or instability of services' organizational structure and patient- and therapist-initiated discontinuation of therapy in routine mental health. METHOD: Three groups, comprising altogether 750 cases in routine mental health care in eight different clinics, were included: cases with patient-initiated discontinuation, therapist-initiated discontinuation, and patients remaining in treatment. Multilevel multinomial regression was used to estimate three models: An initial, unconditional intercept-only model, another one including patient variables, and a final model with significant patient and therapist variables including the organizational stability of the therapists' clinic. RESULTS: High between-therapist variability was noted. Odds ratios and significance tests indicated a strong association of organizational instability with patient-initiated premature termination in particular. CONCLUSIONS: The question of how organizational factors influence the treatment results needs further research. Future studies have to be designed in ways that permit clinically meaningful subdivision of the patients' and the therapists' decisions for premature termination.