Consistent and effective method to define the mouse estrous cycle stage by a deep learning-based model.

The mouse estrous cycle is divided into four stages: proestrus (P), estrus (E), metestrus (M), and diestrus (D). The estrous cycle affects reproductive hormone levels in a wide variety of tissues. Therefore, to obtain reliable results from female mice, it is important to know the estrous cycle stage during sampling. The stage can be analyzed from a vaginal smear under a microscope. However, it is time-consuming, and the results vary between evaluators. Here, we present an accurate and reproducible method for staging the mouse estrous cycle in digital whole-slide images (WSIs) of vaginal smears. We developed a model using a deep convolutional neural network (CNN) in a cloud-based platform, Aiforia Create. The CNN was trained by supervised pixel-level multiclass semantic segmentation of image features from 171 hematoxylin-stained samples. The model was validated by comparing the results obtained by CNN with those of four independent researchers. The validation data included three separate studies comprising altogether 148 slides. The total agreement attested by the Fleiss kappa value between the validators and the CNN was excellent (0.75), and when D, E, and P were analyzed separately, the kappa values were 0.89, 0.79, and 0.74, respectively. The M stage is short and not well defined by the researchers. Thus, identification of the M stage by the CNN was challenging due to the lack of proper ground truth, and the kappa value was 0.26. We conclude that our model is reliable and effective for classifying the estrous cycle stages in female mice.

Is there a shared genetic basis and causal relationship between polycystic ovary syndrome and psychiatric disorders: evidence from a comprehensive genetic analysis.

STUDY QUESTION: Is there a shared genetic basis or causal relationship between polycystic ovary syndrome (PCOS) and a range of psychiatric disorders? SUMMARY ANSWER: Genome-wide genetic correlation analysis and bidirectional Mendelian randomisation (MR) analysis suggest no shared genetic basis or causal relationship of PCOS with psychiatric disorders including depression, anxiety, schizophrenia and bipolar disorder. WHAT IS KNOWN ALREADY: The comorbidity of PCOS with a range of psychiatric disorders has been recognised by epidemiological investigations yet a causal relationship remains unclear. Understanding of how genetic variations contribute to the susceptibility to PCOS and psychiatry disorders could provide meaningful insights into disease mechanisms. STUDY DESIGN, SIZE, DURATION: We incorporated summary statistics from the hitherto largest genome-wide association studies (GWAS) conducted in subjects with PCOS (Ncase = 9322) or four common psychiatric disorders (depression, anxiety, schizophrenia and bipolar disorder) (Ncase ranges between 20 352 and 246 363), all of European ancestry. PARTICIPANTS/MATERIALS, SETTING, METHODS: We quantified pairwise genetic correlation to understand the shared genetic predisposition using genome-wide genetic variants. We performed a two-sample bidirectional Mendelian randomisation analysis to make causal inferences, using GWAS-identified 102 depression-associated genetic instruments, 6 anxiety-associated instruments, 179 schizophrenia-associated instruments, 30 bipolar disorder-associated instruments and 14 PCOS-associated instruments. We performed several important sensitivity analyses examining sex hormones and utilising different MR approaches. MAIN RESULTS AND THE ROLE OF CHANCE: We did not find significant genetic correlations (rg) for PCOS with psychiatric disorders (depression (rg = 0.09, P = 0.06), anxiety (rg = 0.15, P = 0.06), schizophrenia (rg = 0.02, P = 0.59), bipolar disorder (rg = 0.08, P = 0.19)). Genetic predisposition to PCOS was associated with depression in some of our MR approaches, without any evidence of pleiotropy (PMR-Egger intercept = 0.60). However, this weak PCOS-depression causal association attenuated to null after adjusting for BMI (1.00 (0.99-1.02), P = 0.28). On the contrary, we did not observe any statistically significant association between genetically instrumented PCOS with other psychiatric disorders (anxiety 1.01 (0.93-1.08), P = 0.89; schizophrenia 1.03 (0.97-1.10), P = 0.37; bipolar disorder 0.96 (0.90-1.03), P = 0.26). Bidirectional MR did not reveal an effect by which mental health conditions influenced PCOS risk. LIMITATIONS, REASONS FOR CAUTION: Despite our study being the largest in sample size of its kind, the overall negligible causal relationship between PCOS and psychiatric outcomes may reflect a true null association but may also be due to a true effect too modest to be detected. We were not able to investigate PCOS subtypes and used an overall heterogenous PCOS sample due to limited availability of data. WIDER IMPLICATIONS OF THE FINDINGS: Our comprehensive analysis does not identify a shared genetic basis of PCOS with psychiatric diseases. Although genetically instrumented PCOS appears to correlate with depression, such an effect is likely mediated by BMI, suggesting a role of non-genetic exposures underlying the observed comorbidity. STUDY FUNDING/COMPETING INTEREST(S): The work was supported by the Swedish Medical Research Council 2018-02435 (to E.S.V.), Novo Nordisk Foundation NNF19OC0056647 (to E.S.V.), the Adlerbert Research Foundation (to E.S.V.), the SRP in Diabetes at Karolinska Institutet (to E.S.V.) and the Swedish Research Council VR 2018-02247 (to X.J.). The funders had no influence on the data collection, analyses or conclusions of the study. No conflict of interests to declare. TRIAL REGISTRATION NUMBER: N/A.

Changes in HbA1c and circulating and adipose tissue androgen levels in overweight-obese women with polycystic ovary syndrome in response to electroacupuncture.

AIM: Insulin sensitivity is ~40% lower in women with polycystic ovary syndrome (PCOS) than in controls. We tested the hypothesis that 5 weeks of electroacupuncture treatment improves glucose regulation and androgen levels in overweight/obese women with PCOS. MATERIAL AND METHODS: Seventeen women with PCOS, aged 18 to 38 years, with a body mass index (BMI) ≥25 kg/m2 and diagnosed with PCOS were included in this experimental and feasibility study and subjected to five weeks of electroacupuncture treatments three times/week. The primary outcome was changes in whole-body glucose homeostasis measured by euglycemic hyperinsulinemic clamp before and after the intervention. Secondary outcome were changes in HbA1c, circulating catecholamines, adipocyte size and adipose tissue expression of sex steroids and nerve growth factor (NGF). RESULTS: No significant change in glucose homeostasis was observed, but HbA1c decreased by 9.5% (p = 0.004), circulating testosterone decreased by 22% (p = 0.0007) and dihydrotestosterone decreased by 12% (p = 0.007). The two vagal activity markers of plasma serotonin levels and the dopamine metabolite homovanillic acid decreased by 21% (p = 0.027) and 20% (p = 0.011), respectively. Adipose tissue concentrations of testosterone decreased by 18% (p = 0.049), and androstenedione decreased by 13% (p = 0.035), and mature NGF/proNGF ratio, a marker of sympathetic activity, increased (p = 0.04). These changes occurred without changes in anthropometrics. CONCLUSION: Five weeks of electroacupuncture treatment improves HbA1c and circulating and adipose tissue androgens in women with PCOS. This effect is mediated, at least in part, via modulation of vagal activity and adipose tissue sympathetic activity. Based on these findings, we have recently initiated a randomized controlled study (NTC02647827).

Placental STAT3 signaling is activated in women with polycystic ovary syndrome.

STUDY QUESTION: Does polycystic ovary syndrome (PCOS) in women without pregnancy complications affect placental signal transducer and activator of transcription 3 (STAT3) and mechanistic target of rapamycin (mTOR) signaling? SUMMARY ANSWER: Placental STAT3 signaling is activated but mTOR signaling is unaffected in PCOS. WHAT IS KNOWN ALREADY: Women with PCOS have increased risk of poor pregnancy outcomes (e.g. restricted or accelerated fetal growth), indicating placental dysfunction. Placental STAT3 and mTOR pathways regulate placental function and indirectly affect fetal growth. STUDY DESIGN, SIZE, DURATION: In a case-control study, placental tissue and maternal blood were collected at delivery from 40 control pregnant women and 38 PCOS women with uncomplicated pregnancy. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with PCOS were recruited at two medical centers and pregnant controls were recruited at one of these centers. Placental mRNA expression of genes encoding proteins related to steroid action, metabolic pathways and cytokines was analyzed by quantitative RT-PCR. Phosphorylated placental STAT3 (P-STAT3) and mTOR targets was measured by western blot. Levels of sex steroids in serum were determined by mass spectrometry. MAIN RESULTS AND THE ROLE OF CHANCE: Placental P-STAT3 (Tyr-705) was increased in women with PCOS (P < 0.05) versus controls. Placental mTOR signaling was not affected in PCOS women when compared with controls. Circulating levels of androstenedione, androst-5-ene-3ß, 17ß-diol, testosterone, 5α-dihydrotestosterone and etiocholanolone glucuronide were higher and estradiol lower in women with PCOS than in controls (all P < 0.05). No correlation between sex steroid levels in serum and P-STAT3 was observed. LIMITATIONS, REASONS FOR CAUTION: Women with PCOS and pregnancy complications were excluded to avoid the confounding effects of placental pathologies, which could modify STAT3 and mTOR signaling. Moreover, 97.4% of women with PCOS in the study displayed oligoamenorrhea at diagnosis. Thus, the current findings could be restricted to PCOS women with the oligo-anovulatory phenotype without pregnancy complications. WIDER IMPLICATIONS OF THE FINDINGS: Phosphorylation of STAT3 is increased in the placenta from women with PCOS and uncomplicated pregnancies, indicating that specific metabolic placental pathways are activated in the absence of obstetric and perinatal complications. STUDY FUNDING/COMPETING INTERESTS: The work was supported by the Swedish Medical Research Council (Project No. 2011-2732 and 2014-2775); Jane and Dan Olsson Foundation, Wilhelm and Martina Lundgrens's Science Fund; Hjalmar Svensson Foundation (E.S.-V and M.M.); Adlerbert Research Foundation; Swedish federal government under the LUA/ALF agreement ALFFGBG-136481 and 429501 and the Regional Research and Development agreement (VGFOUREG-5171, -11296 and -7861). MM thanks the Becas Chile Programme (Chile) and University of Chile for financial support through a postdoctoral fellowship. There are no competing interests.

Beneficial metabolic effects of the Malaysian herb Labisia pumila var. alata in a rat model of polycystic ovary syndrome.

AIM OF THE STUDY: New options are needed to prevent and treat metabolic disorders associated with polycystic ovary syndrome (PCOS). Labisia pumila var. alata (LPva)-a Malaysian herb thought to have phytoestrogenic effects-has shown promise in reducing body weight gain in ovariectomized rats. In this study, we investigated the effect of LPva on body composition and metabolic features in female rats treated continuously with dihydrotestosterone, starting before puberty, to induce PCOS. MATERIAL AND METHODS: At 9 weeks of age, the PCOS rats were randomly subdivided into two groups; PCOS LPva and PCOS control. PCOS LPva rats received a daily oral dose of LPva (50mg/kg body weight), dissolved in 1 ml of deionised water, for 4-5 weeks. PCOS controls received 1 ml of deionised water on the same schedule. RESULTS: LPva increased uterine weight (27%) and insulin sensitivity (36%) measured by euglycemic hyperinsulinemic clamp. Plasma resistin levels were increased and lipid profile was improved in LPva rats. In adipose tissue, LPva decreased leptin mRNA expression but did not affect expression of resistin and adiponectin. No effects on body composition, adipocyte size, or plasma leptin levels were observed. CONCLUSION: LPva increases uterine weight, indicating estrogenic effects, and improves insulin sensitivity and lipid profile in PCOS rats without affecting body composition.

Anxiety and depression symptoms in women with polycystic ovary syndrome compared with controls matched for body mass index.

BACKGROUND: Anxiety and depression are more prevalent in women with polycystic ovary syndrome (PCOS) than in those without this disorder. Possible confounding effects of overweight and obesity are suggested. The aim was to compare symptoms of anxiety and depression in women with PCOS and controls matched for age, body weight and body mass index (BMI). METHODS: Women with PCOS (n = 30) and controls (n = 30) were recruited from the community. Persons with ongoing psychotropic medication were excluded. All potential participants underwent gynecological examination to confirm case-control status. Participants completed the self-reported versions of the Brief Scale for Anxiety (BSA-S) and Montgomery Asberg Depression Rating Scale (MADRS-S). RESULTS: Women with PCOS had a higher BSA-S score compared with controls (median, range: 10.5, 1-24 versus 5.0, 0-28, P < 0.001). They scored higher on the following four individual symptoms: reduced sleep (2.0, 0-5 versus 0, 0-2, P < 0.001), worry (1.5, 0-4 versus 0, 0-6, P = 0.004), phobias (1, 0-4 versus 0, 0-3, P < 0.001), and pain (1, 0-3 versus 0, 0-2, P < 0.001). No statistical difference was demonstrated regarding MADRS-S scores (10.0, 0-27 versus 5.5, 0-24, P = 0.053). Only one of the nine MADRS-S symptoms, reduced sleep, which is also included in the BSA-S, differed between cases and controls. CONCLUSIONS: Several anxiety symptoms distinguished women with PCOS from a control group matched on BMI. A better understanding of the symptoms is needed to identify and alleviate anxiety symptoms in this vulnerable group.

The effect of massage on immune function and stress in women with breast cancer--a randomized controlled trial.

OBJECTIVES: To examine the short-term effects of light pressure effleurage on circulating lymphocytes by studying the number and activity of peripheral blood natural killer (NK) cells in patients with breast cancer compared to a control group. Furthermore, the effect of light pressure effleurage on salivary cortisol levels, heart rate and blood pressure was studied. DESIGN: Single centre, prospective, randomized and controlled study. METHODS: Thirty women, aged 50 to 75 years (mean 61 sd=7.2) with breast cancer undergoing radiation therapy in a hospital in southwestern Sweden were enrolled in the study. They were allocated to either receive massage in the form of a full-body light pressure effleurage treatment, or a control visit where they were given an equal amount of attention. Blood samples, saliva, notation of heart rate and blood pressure were collected before and after massage/control visit. Differences in change over time between groups were analyzed by Student's t-test. RESULTS: Light pressure effleurage massage decreased the deterioration of NK cell activity occurring during radiation therapy. Furthermore it lowered heart rate and systolic blood pressure. No effects were demonstrated on cortisol and diastolic pressure. CONCLUSIONS: A single full-body light pressure effleurage massage has a short-term effect on NK cell activity, systolic blood pressure and heart rate in patients with breast cancer. However, the long-term clinical importance of these findings needs to be further investigated.

Influence of herring (Clupea harengus) and herring fractions on metabolic status in rats fed a high energy diet.

AIM: Few dietary studies have looked beyond fish oil to explain the beneficial metabolic effects of a fish-containing diet. Our aim was to study whether addition of herring, or sub-fractions of herring, could counteract negative metabolic effects known to be induced by a high-fat, high-sugar diet. METHODS: Rats were given six different diets: standard pellets; high energy diet with chicken mince (HiE control); high energy diet with herring mince (HiE herring); and high energy diet with chicken mince and either herring oil (HiE herring oil), herring press juice, PJ (HiE PJ) or herring low molecular weight PJ (HiE LMW-PJ). Factors associated with the metabolic syndrome were measured. RESULTS: There were no differences in energy intake or body weight between the groups, but animals fed high energy diets had a higher body fat content compared with the pellet group, although not statistically significant in all groups. Mesenteric adipocyte size was smaller in the HiE herring oil group compared with the HiE control. Glucose clamp studies showed that, compared with the pellet group, the HiE control and HiE herring diets, but not the HiE herring oil diet, induced insulin resistance. Addition of herring or herring oil to the high energy diet decreased total cholesterol levels, triacylglycerols and the atherogenic index compared with the HiE control group. CONCLUSIONS: The results suggest that addition of herring or herring oil counteracts negative effects on blood lipids induced by a high energy diet. The lipid component of herring thus seems to be responsible for these beneficial effects.

Acupuncture as an adjunct to standard treatment for pelvic girdle pain in pregnant women: randomised double-blinded controlled trial comparing acupuncture with non-penetrating sham acupuncture.

OBJECTIVE: To investigate whether acupuncture has a greater treatment effect than non-penetrating sham acupuncture in women with pelvic girdle pain (PGP) during pregnancy. DESIGN: Randomised double-blinded controlled trial. SETTING: East Hospital, Gothenburg, and 25 antenatal primary care units in the region of Västra Götaland, Sweden. POPULATION: A total of 115 pregnant women with a clinical diagnosis of PGP who scored > or =50 on a 100-mm visual analogue scale (VAS). METHOD: Women were randomly allocated to standard treatment plus acupuncture or to standard treatment plus non-penetrating sham acupuncture for 8 weeks. MAIN OUTCOME MEASURES: Main outcome measure was pain. Secondary outcomes were frequency of sick leave, functional status, discomfort of PGP, health-related quality of life and recovery of severity of PGP as assessed by the independent examiner. RESULTS: After treatment, median pain decreased from 66 to 36 in the acupuncture group and from 69 to 41 in the non-penetrating sham group (P = 0.493) as assessed on a VAS. Women in the acupuncture group were in regular work to a higher extent than women in the sham group (n = 28/57 versus 16/57, P = 0.041). The acupuncture group had superior ability to perform daily activities measured with the disability rating index (DRI) (44 versus 55, P = 0.001). There were no significant differences in quality of life, discomfort of PGP and recovery from severity of PGP between the groups. CONCLUSIONS: Acupuncture had no significant effect on pain or on the degree of sick leave compared with non-penetrating sham acupuncture. There was some improvement in performing daily activities according to DRI. The data imply that needle penetration contributes to a limited extent to the previously reported beneficial effects of acupuncture.

The effect of massage on cellular immunity, endocrine and psychological factors in women with breast cancer -- a randomized controlled clinical trial.

OBJECTIVES: The purpose of this study was to examine the effect of repeated effleurage massage treatments compared with a visit control group on circulating lymphocytes by studying the number and activity of peripheral blood NK cells, CD4+ and CD8+ T cells in women with breast cancer. Furthermore, the effect of repeated effleurage massage treatments on the levels of cortisol in saliva and oxytocin in plasma as well as degree anxiety, depression and quality of life was studied. DESIGN: A single centre, prospective, randomized, controlled trial. SETTINGS/LOCATION: The study was conducted in a radiation department, in a hospital in south-western Sweden. SUBJECTS: Twenty-two women (mean age=62) with breast cancer undergoing radiation were included in this study. INTERVENTIONS: The patients were randomly assigned to effleurage massage therapy (20 min of effleurage on ten occasions) or to control visits (ten 20-minute visits). OUTCOME MEASURES: Blood samples were collected before the first and last massage/control visit for analysis of peripheral blood NK, T cells and oxytocin. Saliva was analysed for cortisol. In addition, the patients completed the Hospital Anxiety and Depression Scale, Life Satisfaction Questionnaire and Spielbergers State Trait Anxiety Inventory prior to the first and last massage/control visit. RESULTS: Effleurage massage treatment had no significant effect on the number, frequencies or activation state of NK cells or CD4+ or CD8+ T cells. Furthermore, no significant changes between groups were detected on cortisol and oxytocin concentrations, anxiety, depression or quality of life. CONCLUSIONS: Significant effect of effleurage massage on cellular immunity, cortisol, oxytocin, anxiety, depression or quality of life could not be demonstrated in this study. Several possible explanations to the results of this study are discussed.

Acupuncture in polycystic ovary syndrome: current experimental and clinical evidence.

This review describes the aetiology and pathogenesis of polycystic ovary syndrome (PCOS) and evaluates the use of acupuncture to prevent and reduce symptoms related with PCOS. PCOS is the most common female endocrine disorder and it is strongly associated with hyperandrogenism, ovulatory dysfunction and obesity. PCOS increases the risk for metabolic disturbances such as hyperinsulinaemia and insulin resistance, which can lead to type 2 diabetes, hypertension and an increased likelihood of developing cardiovascular risk factors and impaired mental health later in life. Despite extensive research, little is known about the aetiology of PCOS. The syndrome is associated with peripheral and central factors that influence sympathetic nerve activity. Thus, the sympathetic nervous system may be an important factor in the development and maintenance of PCOS. Many women with PCOS require prolonged treatment. Current pharmacological approaches are effective but have adverse effects. Therefore, nonpharmacological treatment strategies need to be evaluated. Clearly, acupuncture can affect PCOS via modulation of endogenous regulatory systems, including the sympathetic nervous system, the endocrine and the neuroendocrine system. Experimental observations in rat models of steroid-induced polycystic ovaries and clinical data from studies in women with PCOS suggest that acupuncture exert long-lasting beneficial effects on metabolic and endocrine systems and ovulation.

Chronic tension-type headache treated with acupuncture, physical training and relaxation training. Between-group differences.

The aim of this study was to compare acupuncture, relaxation training and physical training in the treatment of chronic tension-type headache (CTTH). The study comprised 90 consecutive patients with CTTH who were randomly allocated to acupuncture, relaxation training or physical training. Headache intensity, headache-free days and headache-free periods were registered using a visual analogue scale and a headache diary. The measurements were made 4 weeks before, immediately after, and 3 and 6 months after the treatment period. Immediately after the last treatment, the number of headache-free periods and of headache-free days was higher in the relaxation group compared with the acupuncture group. There were no other significant differences between the groups at any time point. The clinical implications of our findings are that relaxation training induced the most pronounced effects directly after the treatment period, compared with acupuncture and physical training.

The perception of pain and pain-related cognitions in subacute whiplash-associated disorders: its influence on prolonged disability.

PURPOSE: To clarify the relations between the sensory, affective and cognitive dimensions of pain and to analyse what influence these components have on persistent disability in patients with subacute whiplash-associated disorders (WAD). METHOD: The data was obtained from an on-going randomised controlled trial (RCT) on 47 patients. The sensory dimension of pain was evaluated with a visual analogue scale (VAS) diary and a Painometer. The affective dimension was assessed using the Painometer. The Tampa Scale for Kinesiophobia (TSK) and the Self-Efficacy Scale (SES) were used as measures of pain-related cognitions. The Pain Disability Index (PDI) was used as the outcome measure. RESULTS: Forty patients (85%) completed the trial. The correlations between the sensory and affective dimensions of pain were non-significant, which indicates that they are two independent constructs that describe various dimensions of whiplash-related pain. High pain intensity and pain affect, more widespread pain, and high fear of movement/(re)injury corresponded to low self-efficacy. Multiple regression analyses showed that self-efficacy was the most important predictor of persistent disability contributing to 42% of the variation in the PDI score. CONCLUSION: The treatment approach for patients with subacute WAD should incorporate the multidimensional nature of pain and to prevent disability special effort should be made to enhance the patient's self-efficacy beliefs.

Effect of exercise on ovarian morphology and expression of nerve growth factor and alpha(1)- and beta(2)-adrenergic receptors in rats with steroid-induced polycystic ovaries.

Oestadiol valerate (EV)-induced polycystic ovaries (PCO) in rats cause anovulation and cystic ovarian morphology. Denervation of ovarian sympathetic nerves restores ovulatory disruption. In the present study, we determined whether 5 weeks of voluntary exercise influence ovarian morphology and the expression of sympathetic markers in the EV-induced PCO rat model. The effect of exercise on (i) ovarian morphology; (ii) mRNA and protein expression of nerve growth factor (NGF); and (iii) mRNA and number of ovarian-expressing cells for the NGF receptor (p75 neurotrophin receptor) and the alpha(1a)-, alpha(1b)-, alpha(1d)- and beta(2)-adrenergic receptors (ARs) in rats with EV-induced PCO was evaluated. PCO was induced by a single i.m. injection of EV, and controls were injected with oil alone in adult cycling rats. The rats were divided into four groups: (i) control (oil); (ii) exercise group (oil + exercise); (iii) a PCO group (EV); and (iv) a PCO exercise group (EV + exercise). The exercise and PCO exercise groups ran voluntarily for 5 weeks in computer-monitored wheels placed in the cages where they were housed. The results obtained indicated that ovarian morphology was almost normalised in the PCO exercise group; NGF mRNA and protein concentrations were normalised in the PCO exercise group; high numbers of NGF receptor expressing cells in PCO ovaries were lowered by exercise; and the number of immunopositive cells of the different AR subtypes were all reduced after exercise in the PCO group, except for the alpha(1b)- and beta(2)-AR whereas the mRNA levels were unaffected, indicating transcriptional regulation. In conclusion, our data indicate a beneficial effect of regular exercise, as a modulator of ovarian sympathetic innervation, in the prevention and treatment of human PCOS.

Neck pain and disability following motor vehicle accidents--a cohort study.

The primary aim of the study was to compare the prevalence of neck pain and disability in a group exposed to motor vehicle accidents (MVAs) with those in the general population. The secondary aim was to assess the prevalence of a past history of exposure to an MVA with sequelae of neck pain in the general population. The exposed group consisted of 121 patients with neck complaints following an MVA in 1983. The control group, consisting of 1,491 subjects, was randomly selected, with attention to the distribution of age and gender in the exposed group. A neck-pain questionnaire was mailed to the subjects. In the control group, it included enquiry about a history of exposure to an MVA with sequelae of neck pain. The Neck Disability Index (NDI) was used to assess neck-related disability. In the exposed group 108 subjects (89%) responded, and in the control group 931 (62%) did. Seventeen years after the MVA, 59 subjects (55%) reported neck pain in the exposed group, with no gender differences. In the control group 270 (29%) reported neck pain with a higher frequency among women (34%) than men (19%) (p<0.01). There was a significant difference between the exposed group and the control group regarding the occurrence of neck pain (p<0.001). In the control group 34% recalled a history of an MVA, among whom one-third reported neck pain in connection with the accident and 28% had persistent neck pain referable to the accident. The exposed group scored significantly higher on the NDI (p<0.001) and reported significantly higher neck pain intensity than did the control group (p<0.001). In conclusion, a past history of exposure to an MVA with sequelae of neck pain appears to have a substantial impact on future persistent neck pain and associated disability.

Effects of electro-acupuncture on corticotropin-releasing factor in rats with experimentally-induced polycystic ovaries.

The aims of the present study were to investigate corticotropin-releasing factor (CRF) concentrations in the brain, the adrenal glands, and the ovaries in rats with estradiol valerate (EV) induced polycystic ovaries (PCO). The effect of 12 electro-acupuncture (EA) treatments on CRF concentrations was also investigated. The CRF concentrations in the median eminence (ME) were significantly increased in rats with PCO (both the PCO control group and the PCO group receiving EA) compared with the healthy control group (veichle control group), indicating increased activity in the hypothalamus-pituitary axis. The CRF concentrations in the ovaries were significantly reduced in the PCO group receiving EA compared with the PCO control group. Also, there was a decrease in comparison withthe healthy control group but the decrease was not as significant. This finding indicates that repeated EA treatments change the neuroendocrinological state in the ovaries, which may play an important role in reproductive failure.

Effects of electro-acupuncture on nerve growth factor and ovarian morphology in rats with experimentally induced polycystic ovaries.

Despite extensive research on the pathogenesis of polycystic ovary syndrome (PCOS), there is still disagreement on the underlying mechanisms. The rat model for experimentally induced polycystic ovaries (PCO)-produced by a single injection of estradiol valerate-has similarities with human PCOS, and both are associated with hyperactivity in the sympathetic nervous system. Nerve growth factor (NGF) is known to serve as a neurotrophin for both the sympathetic and the sensory nervous systems and to enhance the activity of catecholaminergic and possibly other neuron types. Electro-acupuncture (EA) is known to reduce hyperactivity in the sympathetic nervous system. For these reasons, the model was used in the present study to investigate the effects of EA (12 treatments, approximately 25 min each, over 30 days) by analyzing NGF in the central nervous system and the endocrine organs, including the ovaries. The main findings in the present study were first, that significantly higher concentrations of NGF were found in the ovaries and the adrenal glands in the rats in the PCO model than in the control rats that were only injected with the vehicle (oil or NaCl). Second, that repeated EA treatments in PCO rats resulted in concentrations of NGF in the ovaries that were significantly lower than those in non-EA-treated PCO rats but were within a normal range that did not differ from those in the untreated oil and NaCl control groups. The results in the present study provide support for the theory that EA inhibits hyperactivity in the sympathetic nervous system.

Effects of electro-acupuncture on anovulation in women with polycystic ovary syndrome.

BACKGROUND: The present study was designed to evaluate if electro-acupuncture (EA) could affect oligo-/anovulation and related endocrine and neuroendocrine parameters in women with polycystic ovary syndrome (PCOS). METHODS: Twenty-four women (between the ages of 24 and 40 years) with PCOS and oligo-/amenorrhea were included in this non-randomized, longitudinal, prospective study. The study period was defined as the period extending from 3 months before the first EA treatment, to 3 months after the last EA treatment (10-14 treatments), in total 8-9 months. The menstrual and ovulation patterns were confirmed by recording of vaginal bleedings and by daily registrations of the basal body temperature (BBT). Blood samples were collected within a week before the first EA, within a week after the last EA and 3 months after EA. RESULTS: Nine women (38%) experienced a good effect. They displayed a mean of 0.66 ovulations/woman and month in the period during and after the EA period compared to a mean of 0.15 before the EA period (p=0.004). Before EA, women with a good effect had a significantly lower body-mass index (BMI) (p<0.001), waist-to-hip circumference ratio (WHR) (p=0.0058), serum testosterone concentration (p=0.0098), serum testosterone/sex hormone binding globulin (SHBG) ratio (p=0.011) and serum basal insulin concentration (p=0.0054), and a significantly higher concentration of serum SHBG (p=0.040) than did those women with no effect. CONCLUSION: Repeated EA treatments induce regular ovulations in more than one third of the women with PCOS. The group of women with good effect had a less androgenic hormonal profile before treatment and a less pronounced metabolic disturbance compared with the group with no effect. For this selected group EA offers an alternative to pharmacological ovulation induction.

A prospective randomized study of electro-acupuncture versus alfentanil as anaesthesia during oocyte aspiration in in-vitro fertilization.

The aim of the present study was to evaluate the anaesthetic effect during oocyte aspiration of a paracervical block (PCB) in combination with either electro-acupuncture (EA) or intravenous alfentanil. In all, 150 women undergoing in-vitro fertilization (IVF) and embryo transfer were randomized to receive either EA plus PCB or alfentanil plus PCB. Visual analogue scales (VAS) were used to evaluate subjective experiences during oocyte aspiration, and IVF outcome parameters were recorded. No differences in pain directly related to oocyte aspiration, adequacy of anaesthesia during oocyte aspiration, abdominal pain, or degree of nausea were found between the two groups in the VAS ratings. Before oocyte aspiration, the level of stress was significantly higher in the EA group than in the alfentanil group (P < 0.05), and the EA group experienced discomfort for a significantly longer period during oocyte aspiration (P < 0. 01). Compared with the alfentanil group, the EA group had a significantly higher implantation rate (P < 0.05), pregnancy rate (P < 0.05), and take home baby rate (P < 0.05) per embryo transfer. In conclusion, EA has been shown to be as good an anaesthetic method as alfentanil during oocyte aspiration, and we suggest that EA may be a good alternative to conventional anaesthesia during oocyte aspiration.

Reduction of blood flow impedance in the uterine arteries of infertile women with electro-acupuncture.

In order to assess whether electro-acupuncture (EA) can reduce a high uterine artery blood flow impedance, 10 infertile but otherwise healthy women with a pulsatility index (PI) >=3.0 in the uterine arteries were treated with EA in a prospective, non-randomized study. Before inclusion in the study and throughout the entire study period, the women were down-regulated with a gonadotrophin-releasing hormone analogue (GnRHa) in order to exclude any fluctuating endogenous hormone effects on the PI. The baseline PI was measured when the serum oestradiol was <=0.1 nmol/l, and thereafter the women were given EA eight times, twice a week for 4 weeks. The PI was measured again closely after the eighth EA treatment, and once more 10-14 days after the EA period. Skin temperature on the forehead (STFH) and in the lumbrosacral area (STLS) was measured during the first, fifth and eighth EA treatments. Compared to the mean baseline PI, the mean PI was significantly reduced both shortly after the eighth EA treatment (P < 0.0001) and 10-14 days after the EA period (P < 0.0001). STFH increased significantly during the EA treatments. It is suggested that both of these effects are due to a central inhibition of the sympathetic activity.