[Study on construction of c-Met specific CAR-T cells and its killing effect on non-small cell lung carcinoma].

Objective: To produce chimeric antigen receptor T cells (CAR-T) targeting human hepatocyte growth factor/c-Met (HGF/c-Met) protein and detect its cytotoxicity against non-small cell lung cancer (NSCLC) cells H1975 in vitro. Methods: The whole gene sequence of c-Met CAR containing c-Met single-chain fragment variable was synthesized and linked to lentiviral vector plasmid, plasmid electrophoresis was used to detect the correctness of target gene. HEK293 cells were transfected with plasmid and the concentrated solution of the virus particles was collected. c-Met CAR lentivirus was transfected into T cells to obtain second-generation c-Met CAR-T and the expression of CAR sequences was verified by reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) and western blot, and the positive rate and cell subtypes of c-Met CAR-T cells were detected by flow cytometry. The positive expression of c-Met protein in NSCLC cell line H1975 was verified by flow cytometry, and the negative expression of c-Met protein in ovarian cancer cell line A2780 was selected as the control. The cytotoxicity of c-Met CAR-T to H1975 was detected by lactate dehydrogenase (LDH) cytotoxicity assay at 1∶1, 5∶1, 10∶1 and 20∶1 of effector: target cell ratio (E∶T). Enzyme-linked immunosorbent assay (ELISA) was used to detect the release of cytokines such as TNF-α, IL-2 and IFN-γ from c-Met CAR-T co-cultured with H1975. Results: The size of band was consistent with that of designed c-Met CAR, suggesting that the c-Met CAR plasmid was successfully constructed. The results of gene sequencing were consistent with the original design sequence and lentivirus was successfully constructed. CAR molecules expression in T cells infected with lentivirus was detected by western blot and RT-qPCR, which showed c-Met CAR-T were successfully constructed. Flow cytometry results showed that the infection efficiency of c-Met CAR in T cells was over 38.4%, and the proportion of CD8(+) T cells was increased after lentivirus infection. The NSCLC cell line H1975 highly expressed c-Met while ovarian cancer cell line A2780 negatively expressed c-Met. LDH cytotoxicity assay indicated that the killing efficiency was positively correlated with the E∶T, and higher than that of control group, and the killing rate reached 51.12% when the E∶T was 20∶1. ELISA results showed that c-Met CAR-T cells released more IL-2, TNF-α and IFN-γ in target cell stimulation, but there was no statistical difference between c-Met CAR-T and T cells in the non-target group. Conclusions: Human NSCLC cell H1975 expresses high level of c-Met which can be used as a target for immunotherapy. CAR-T cells targeting c-Met have been successfully produced and have high killing effect on c-Met positive NSCLC cells in vitro.

Evaluation of the effects of sire and dam calving group on age at first calving in Brahman heifers.

This study evaluated the possible effects of sire and dam calving groups on age at first calving in Brahman heifers. A total of 570 heifers born between the years 2004 and 2017 were exposed as yearlings to fertile bulls through time of pregnancy determination. A calving group was determined by calculating the mean (993 d) and standard deviation (187 d) of heifer age at first calving. Heifers considered to calve early (≤899 d; calving group = 1) or late (≥1087 d; calving group = 3) were at least half a standard deviation (94 d) away from the mean. All other heifers were considered to have an intermediate age at first calving (900-1086 d; calving group = 2). Of the 570 heifers, only heifers from a dam (n = 182) with a known age at first calving and from a sire (n = 35) with 5 or more daughters were kept to determine the effect of dam calving group and the effect of sire calving group on age at first calving and calving group in daughters, resulting in a total of 284 heifers available for analysis. Variables included were dam and sire calving groups of the heifer, heifer age at first calving, heifer calving group, heifer season of birth, and heifer year of birth. Data were analyzed using the GLM procedures of SAS and proportions were tested using Chi-square. Sire calving group did affect (P < 0.01) age at first calving and calving group in heifers, but dam calving group did not affect (P > 0.10) daughter age at first calving or calving group. Analysis of dam calving group and sire calving group effects identified a year of birth effect (P < 0.01) on daughter age at first calving and calving group, whereas there was no significant season of birth effect. The proportion of daughters calving early for sire calving groups differed significantly from the expected proportion (P < 0.01), whereas the proportion of daughters calving early for dam calving groups did not differ. An effort to produce a greater proportion of Brahman heifers capable of calving early will not be effective from the dam side but may be effective from the sire side.

Maternal nutrient restriction alters endocrine pancreas development in fetal heifers.

Maternal nutrient restriction during pregnancy alters fetal programming, which modifies the growth and health of the offspring in postnatal life. In cattle, nutrient restriction during pregnancy can be a result of environmental or economic factors, but little is known about how it alters the physiology of the fetus and affects future reproductive or growth efficiency. This study used female monozygotic twins, produced through in vitro fertilization and embryo splitting, to determine the effect of moderate maternal nutrient restriction on fetal development. Recipient Angus cross heifers pregnant with one twin were fed a diet meeting 100% National Research Council (NRC) total energy requirements (n = 4; control), whereas recipient heifers pregnant with the second twin were fed at 70% of NRC total energy requirements (n = 4; restricted) from gestational day (GD) 158 to GD 265 in Calan gate feeders. Recipient heifers were killed at GD 265. Change in maternal metabolic body weight was greater from zero in restricted heifers than controls (P < 0.05); restricted heifers lost weight during the nutrient restriction period. There was no difference in last rib back fat or rib eye area between groups (P > 0.10). There was no difference in fetal weight, uterine weight, or total placentome weight between groups (P > 0.10). The pancreas weight was reduced in restricted fetuses compared with control fetuses (P < 0.01), but there were no other differences in fetal organ weights (P > 0.10). Plasma insulin concentrations were reduced in restricted fetuses compared with controls (P < 0.01), but there was no effect of maternal diet on plasma glucose or glucagon concentrations in the fetus (P > 0.10). Histological analyses of the fetal pancreas revealed no differences in endocrine cell number or localization. Results indicate that a modest late gestation nutritional restriction impairs development of the fetal pancreas in the cow. Additional research will be needed to determine if these developmental changes lead to altered glucose and insulin homeostasis in the adult.

The Integrative Migraine Pain Alleviation through Chiropractic Therapy (IMPACT) trial: Study rationale, design and intervention validation.

INTRODUCTION: Approximately 15% of the US population experiences migraine, with women afflicted three times as often as men. While medications are often used as first-line treatments, up to 50% of people with migraine pursue complementary and integrative medicine. One promising non-pharmacological approach for migraine is chiropractic care, due to the co-occurrence of migraine disease and musculoskeletal tension and pain. To date, no large-scale trials have evaluated the impact of a comprehensive model of chiropractic care on migraine. METHODS: The Integrative Migraine Pain Alleviation through Chiropractic Therapy (IMPACT) study is a two-arm pilot pragmatic randomized clinical trial evaluating a multimodal chiropractic care intervention plus enhanced usual care (UC) vs. enhanced UC alone for adult women with episodic migraine. A total of 60 women aged 20-55 who meet criteria for episodic migraine will be randomly assigned to an evidence-informed, musculoskeletal focused multimodal chiropractic care (10 sessions over 14 weeks) plus enhanced UC vs. enhanced UC alone. Enhanced UC includes conventional care, migraine education materials, and biweekly check-in phone calls. Study specific aims include: 1) Determine safety and feasibility of the study design; 2) Provide preliminary data on the effectiveness of chiropractic care on migraine frequency, severity, duration and medication use; and 3) Provide preliminary estimates of the effects of chiropractic care on disability, health-related quality of life, and psychosocial well-being. DISCUSSION: Findings will be used to inform the design of a full-scale trial evaluating chiropractic care for women with episodic migraines.

Diabetes self-management education exposure and glycated haemoglobin levels among Marshallese participants in a randomized controlled study.

AIMS: A randomized control trial (RCT) of diabetes self-management education (DSME), undertaken by a community-based participatory research (CBPR) partnership between the University of Arkansas for Medical Sciences (UAMS) and the Marshallese community in Arkansas. The RCT examined the effect of hours of intervention exposure, with the hypothesis that increased exposure is one reason the Adapted-Family DSME was found to be more effective than the Standard DSME. METHODS: Some 221 Marshallese with type 2 diabetes were randomized to an Adapted-Family DSME group (in-home setting) (n = 110) or a Standard DMSE group (community setting) (n = 111). The Adapted-Family DSME included 10 h of education that covered the core self-care elements recommended by the American Diabetes Association (ADA) and American Association of Diabetes Educators' (AADE) recommendations. The Standard DSME included 10 h of intervention with all ADA and AADE core elements. RESULTS: The number of hours of intervention exposure in the Adapted-Family DSME arm (mean = 8.0; median = 10.0) was significantly higher than the number of hours of intervention received in the Standard DSME arm (mean = 1.5; median = 0.0). As hypothesized, higher exposure was associated with a significant reduction in HbA1c in a model including only study arm and exposure (P = 0.01), and in a model including study arm, exposure, and all demographic variables (P = 0.046). CONCLUSIONS: This finding is consistent with previous reviews that showed increased exposure to DSME produced improved glycaemic control and ≥ 10 h of DSME produces clinically meaningful reductions in HbA1c .

Patient-centered outcomes of high-velocity, low-amplitude spinal manipulation for low back pain: a systematic review.

Low back pain (LBP) is a well-recognized public health problem with no clear gold standard medical approach to treatment. Thus, those with LBP frequently turn to treatments such as spinal manipulation (SM). Many clinical trials have been conducted to evaluate the efficacy or effectiveness of SM for LBP. The primary objective of this paper was to describe the current literature on patient-centered outcomes following a specific type of commonly used SM, high-velocity low-amplitude (HVLA), in patients with LBP. A systematic search strategy was used to capture all LBP clinical trials of HVLA using our predefined patient-centered outcomes: visual analogue scale, numerical pain rating scale, Roland-Morris Disability Questionnaire, and the Oswestry Low Back Pain Disability Index. Of the 1294 articles identified by our search, 38 met our eligibility criteria. Like previous SM for LBP systematic reviews, this review shows a small but consistent treatment effect at least as large as that seen in other conservative methods of care. The heterogeneity and inconsistency in reporting within the studies reviewed makes it difficult to draw definitive conclusions. Future SM studies for LBP would benefit if some of these issues were addressed by the scientific community before further research in this area is conducted.

Production of transgenic calves expressing an shRNA targeting myostatin.

Myostatin (MSTN) is a well-known negative regulator of muscle growth. Animals that possess mutations within this gene display an enhanced muscling phenotype, a desirable agricultural trait. Increased neonatal morbidity is common, however, resulting from complications arising from the birth of offspring with increased fetal muscle mass. The objective of the current research was to generate an attenuated MSTN-null phenotype in a large-animal model using RNA interference to enhance muscle development without the detrimental consequences of an inactivating mutation. To this end, we identified a series of short interfering RNAs that demonstrated effective suppression of MSTN mRNA and protein levels. To produce transgenic offspring capable of stable MSTN suppression in vivo, a recombinant lentiviral vector expressing a short hairpin RNA (shRNA) targeting MSTN for silencing was introduced into bovine fetal fibroblasts. These cells were used as nucleus donors for somatic cell nuclear transfer (SCNT). Twenty blastocysts were transferred into seven recipient cows resulting in five pregnancies. One transgenic calf developed to term, but died following delivery by Caesarean-section. As an alternative strategy, microinjection of recombinant lentiviral particles into the perivitelline space of in vitro-produced bovine zygotes was utilized to produce 40 transgenic blastocysts that were transferred into 14 recipient cows, resulting in 7 pregnancies. Five transgenic calves were produced, of which three expressed the transgene. This is the first report of transgenic livestock produced by direct injection of a recombinant lentivirus, and expressing transgenes encoding shRNAs targeting an endogenous gene (myostatin) for silencing.

Cryopreservation of in vitro produced bovine embryos: effects of lipid segregation and post-thaw laser assisted hatching.

The objective was to determine if lipid segregation, with or without post-thaw laser assisted hatching (LAH) of in vitro produced (IVP) bovine embryos, would enhance in vitro survivability and development 24 h post-thaw. On Day 6 of culture (Day 0 = IVF), in vitro produced bovine embryos were divided into three developmental stages: 32-cell (n = 78), compact morula (CM n = 223), and blastocyst (n =56). Embryos within each stage were allocated to the following treatments prior to cryopreservation in 1.5M ethylene glycol: no treatment (Control), 7.5 µg/mL Cytochalasin B for 20 min (CB), or CB with centrifugation (16,000 × g) for 20 min (CBCF). All CB treatments were extended to include embryo freezing. Immediately post-thaw, one-half of the CBCF and Control groups were subjected to zona pellucida drilling (LAH), using the XY Clone® system, creating groups CBCFLAH and LAH, respectively. All thawed embryos were cultured for 24 h and evaluated. No treatment differences were observed for either post-thaw survival or 24 h development. Within the CM stage, CBCFLAH and LAH exhibited a greater number of both total and live cells than Control (total: 69.4, 69.3, 53.0, live: 56.4, 54.7, 39.3 respectively; P < 0.05). In conclusion, LAH post-thaw alone or in combination with CBCF improved embryo viability following cryopreservation.

Clinical and molecular characterization of a re-established line of sheep exhibiting hemophilia A.

BACKGROUND: Large animal models that accurately mimic human hemophilia A (HA) are in great demand for developing and testing novel therapies to treat HA. OBJECTIVES: To re-establish a line of sheep exhibiting a spontaneous bleeding disorder closely mimicking severe human HA, fully characterize their clinical presentation, and define the molecular basis for disease. PATIENTS/METHODS: Sequential reproductive manipulations were performed with cryopreserved semen from a deceased affected ram. The resultant animals were examined for hematologic parameters, clinical symptoms, and responsiveness to human FVIII (hFVIII). The full coding region of sheep FVIII mRNA was sequenced to identify the genetic lesion. RESULTS AND CONCLUSIONS: The combined reproductive technologies yielded 36 carriers and 8 affected animals. The latter had almost non-existent levels of FVIII:C and extremely prolonged aPTT, with otherwise normal hematologic parameters. These animals exhibited bleeding from the umbilical cord, prolonged tail and nail cuticle bleeding time, and multiple episodes of severe spontaneous bleeding, including hemarthroses, muscle hematomas and hematuria, all of which responded to hFVIII. Inhibitors of hFVIII were detected in four treated animals, further establishing the preclinical value of this model. Sequencing identified a premature stop codon and frame-shift in exon 14, providing a molecular explanation for HA. Given the decades of experience using sheep to study both normal physiology and a wide array of diseases and the high homology between human and sheep FVIII, this new model will enable a better understanding of HA and facilitate the development and testing of novel treatments that can directly translate to HA patients.

New commercial opportunities for advanced reproductive technologies in horses, wildlife, and companion animals.

As advanced reproductive technologies become more efficient and repeatable in livestock and laboratory species, new opportunities will evolve to apply these techniques to alternative and non-traditional species. This will result in new markets requiring unique business models that address issues of animal welfare and consumer acceptance on a much different level than the livestock sector. Advanced reproductive technologies and genetic engineering will be applied to each species in innovative ways to provide breeders more alternatives for the preservation and propagation of elite animals in each sector. The commercialization of advanced reproductive techniques in these niche markets should be considered a useful tool for conservation of genetic material from endangered or unique animals as well as production of biomedical models of human disease.

Prevalence of nonmusculoskeletal complaints in chiropractic practice: report from a practice-based research program.

OBJECTIVE: To identify patient and practice characteristics that might contribute to people's seeking chiropractic care for nonmusculoskeletal complaints. DESIGN: This was a cross-sectional study conducted through the methods of practice-based research. SETTING: Data were collected in 1998--1999 in chiropractic offices in the United States, Canada, and Australia; data were managed by a practice-based research office operating in a chiropractic research center. POPULATION: The subjects were new and established patients of all ages who visited the participating offices during a designated data collection week. DATA ANALYSIS: Multiple logistic regression was used to examine factors associated with patients' presenting for nonmusculoskeletal chief complaints. Pearson's chi(2) test was used to examine associations among practice variables and the proportion of patients with nonmusculoskeletal chief complaints. RESULTS: A total of 7651 patients of 161 chiropractors in 110 practices in 32 states and 2 Canadian provinces participated; data from 2 Australian practices were included in the totals but not in the analysis. Nonmusculoskeletal complaints accounted for 10.3% of the chief complaints. The following characteristics made patients more likely to present with nonmusculoskeletal chief complaints: being less than 14 years of age (adjusted odds ratio [AOR], 6.9; 95% CI, 5.2--9.1); being female (AOR, 1.5; CI, 1.3--1.8); presenting in a small town/rural location (AOR, 1.9; CI, 1.3--2.7); reporting more than 1 complaint, especially nonmusculoskeletal complaints (AOR, 4.9; CI, 3.9--6.0); having received medical care for the chief complaint (AOR, 3.4; CI, 2.9--4.1); and having first received chiropractic care before 1960 (AOR, 1.7; CI, 1.1--2.4). Practices with the highest proportion of patients with nonmusculoskeletal chief complaints (>17%) were less likely to accept insurance and more likely to be in locations with populations greater than 100,000. They used the most common chiropractic adjustive techniques less frequently and used more nonadjustive procedures, especially diet/nutrition counseling, nutritional supplementation, herbal preparations, naturopathy, and homeopathy. CONCLUSIONS: Drawing on practices with the patient and practice characteristics identified in this study to conduct outcomes studies on nonmusculoskeletal conditions is a possible direction for future research.

Cloning to reproduce desired genotypes.

Cloned sheep, cattle, goats, pigs and mice have now been produced using somatic cells for nuclear transplantation. Animal cloning is still very inefficient with on average less than 10% of the cloned embryos transferred resulting in a live offspring. However successful cloning of a variety of different species and by a number of different laboratory groups has generated tremendous interest in reproducing desired genotypes. Some of these specific genotypes represent animal cell lines that have been genetically modified. In other cases there is a significant demand for cloning animals characterized by their inherent genetic value, for example prize livestock, household pets and rare or endangered species. A number of different variables may influence the ability to reproduce a specific genotype by cloning. These include species, source of recipient ova, cell type of nuclei donor, treatment of donor cells prior to nuclear transfer, and the techniques employed for nuclear transfer. At present, there is no solid evidence that suggests cloning will be limited to only a few specific animals, and in fact, most data collected to date suggests cloning will be applicable to a wide variety of different animals. The ability to reproduce any desired genotype by cloning will ultimately depend on the amount of time and resources invested in research.

Evidence for placental abnormality as the major cause of mortality in first-trimester somatic cell cloned bovine fetuses.

The production of cloned animals is, at present, an inefficient process. This study focused on the fetal losses that occur between Days 30-90 of gestation. Fetal and placental characteristics were studied from Days 30-90 of gestation using transrectal ultrasonography, maternal pregnancy specific protein b (PSPb) levels, and postslaughter collection of fetal tissue. Pregnancy rates at Day 30 were similar for recipient cows carrying nuclear transfer (NT) and control embryos (45% [54/120] vs. 58% [11/19]), although multiple NT embryos were often transferred into recipients. From Days 30-90, 82% of NT fetuses died, whereas all control pregnancies remained viable. Crown-rump (CR) length was less in those fetuses that were destined to die before Day 90, but no significant difference was found between the CR lengths of NT and control fetuses that survived to Day 90. Maternal PSPb levels at Days 30 and 50 of gestation were not predictive of fetal survival to Day 90. The placentas of six cloned and four control (in vivo or in vitro fertilized) bovine pregnancies were compared between Days 35 and 60 of gestation. Two cloned placentas showed rudimentary development, as indicated by flat, cuboidal trophoblastic epithelium and reduced vascularization, whereas two others possessed a reduced number of barely discernable cotyledonary areas. The remaining two cloned placentas were similar to the controls, although one contained hemorrhagic cotyledons. Poor viability of cloned fetuses during Days 35-60 was associated with either rudimentary or marginal chorioallantoic development. Our findings suggest that future research should focus on factors that promote placental and vascular growth and on fetomaternal interactions that promote placental attachment and villous formation.

Chiropractic care for patients aged 55 years and older: report from a practice-based research program.

OBJECTIVE: To characterize patients aged 55 years and older and features of chiropractic care provided to them. DESIGN: Observational, practice-based research study. SETTING: Chiropractic offices in the United States and Canada, 1997-1998. PARTICIPANTS: Chiropractors in 96 practices in 32 states and two Canadian provinces collected data on 805 eligible patients aged 55 years and older during a 12-week study period. MEASUREMENTS: In addition to questionnaires on practice characteristics, patient demographics, chief complaints, and health habits, two standardized instruments were administered: for general health status, the Medical Outcomes Study 12-Item Short-Form Health Survey (SF-12); and for disability related to chronic pain, the Pain Disability Index (PDI). RESULTS: Of 805 study patients, 60.1% were women and' 94.7% were white. Overweight patients comprised 38.6% and obese 20.6% (n = 656) of the total; 9.7% of patients were hypertensive (n = 590). Smoking was reported by 12.7% and 50.2% reported regular exercise. The Physical Component Summary scores of the SF-12 seemed somewhat lower than population norms, whereas the Mental Component Summary scores differed very little from norms. Chief complaints were predominantly pain-related (72.3%), most commonly back pain (32.9%). The PDI mean baseline score for chronic patients was 16.3 (scale, 0-70), and 40.6% of study patients reported using at least one pain medication (prescription or nonprescription) more than three times per week. More than half of complaints (54.9%) had onsets more than 6 weeks before the baseline visit. For 66.6% of subjects, a chiropractor was the only provider for their current complaint. In addition to manipulation, most common features of care were recommendations on exercise (41.0%), heat or cold applications (40.8%), and food supplements (24.5%). At 4 weeks, 19.6% were discharged, 58.8% continued treatment, and 20.1% had discontinued care (self-discharged). For these three groups, those with higher PDI mean baseline scores showed more change at 4 weeks. For patients who were discharged by the doctor, the proportion of reported pain medication use decreased 7.3% from baseline to 4 weeks, increased for patients who discontinued care, and remained about the same for those continuing care. CONCLUSIONS: Further investigation of the PDI and a decrease in pain medication use as outcome measures seems warranted. The descriptive information in this study may assist providers of care to older adults to better understand their patients' use of chiropractic care.

Development rates of male bovine nuclear transfer embryos derived from adult and fetal cells.

This study compared the nuclear transfer (NT) embryo development rates of adult and fetal cells within the same genotype. The adult fibroblast cells were obtained from a 21-yr-old Brahman bull. The fetal cells were derived from a Day 40 NT fetus previously cloned using cells from the Brahman bull. Overall, similar numbers of blastocysts developed from both adult (53 of 190; 28%) and fetal (39 of 140; 28%) donor cells. Improved blastocyst development rates were observed when fetal cells were serum-starved (serum-fed 12% vs. serum-starved 43%; P < 0.01) whereas there was no similar benefit when adult cells were serum-starved (both serum-fed and serum-starved 28%). Day 30 pregnancy rates were similar for blastocysts derived from adult (6 of 26; 23%) or fetal (5 of 32; 16%) cells. Day 90 pregnancy rates were 3 of 26 for adult and 0 of 32 for the fetal cell lines. One viable bull calf derived from a 21-yr-old serum-starved adult skin fibroblast was born in August 1999. In summary, somatic NT embryo development rates were similar whether adult or fetal cells, from the same genotype, were used as donor cells. Serum starvation of these adult donor cells did not improve development rates of NT embryos to blastocyst, but when fetal cells were serum-starved, there was a significant increase in development to blastocyst.

Birth of piglets after transfer of embryos cryopreserved by cytoskeletal stabilization and vitrification.

Pig embryos suffer severe sensitivity to hypothermic conditions, which limits their ability to withstand conventional cryopreservation. Research has focused on high lipid content of pig embryos and its role in hypothermic sensitivity, while little research has been conducted on structural damage. Documenting cytoskeletal disruption provides information on embryonic sensitivity and cellular response to cryopreservation. The objectives of this study were to document microfilament (MF) alterations during swine embryo vitrification, to utilize an MF inhibitor during cryopreservation to stabilize MF, and to determine the developmental competence of cytoskeletal-stabilized and vitrified pig embryos. Vitrified morulae/early blastocysts displayed MF disruptions and lacked developmental competence after cryopreservation; hatched blastocysts displayed variable MF disruption and developmental competence. Cytochalasin-b did not improve morula/early blastocyst viability after vitrification; however, it significantly (P < 0.05) improved survival and development of expanded and hatched blastocysts. After embryo transfer, we achieved pregnancy rates of almost 60%, and litter sizes improved from 5 to 7.25 piglets per litter. This study shows that the pig embryo cytoskeleton can be affected by vitrification and that MF depolymerization prior to vitrification improves blastocyst developmental competence after cryopreservation. After transfer, vitrified embryos can produce live, healthy piglets that grow normally and when mature are of excellent fecundity.

Preliminary study of the effects of a placebo chiropractic treatment with sham adjustments.

OBJECTIVE: To identify aspects of the delivery of placebo chiropractic treatments by using sham adjustments that may cause a treatment effect and that may affect the success of blinding. DESIGN AND SETTING: Two-period crossover design in a chiropractic college research clinic. SUBJECTS: Eighteen volunteer staff, students, and faculty of the chiropractic college who reported low-back pain within the last 6 months. INTERVENTIONS: Flexion-distraction technique was used to perform chiropractic adjustments, and a hand-held instrument (Activator adjusting instrument) with the pressure gauge set on the 0 was used to perform sham adjustments. The treatment period was 2 weeks, with a total of 4 visits. MAIN OUTCOME MEASURES: The Visual Analog Scale (VAS) for pain and Global Well-Being Scale (GWBS). RESULTS: Although VAS and GWBS scores improved with both treatments, a somewhat greater improvement occurred in most cases with the active treatment. Eight of 14 patients interviewed believed that the placebo had a treatment effect. CONCLUSION: This study provided preliminary information that was useful in planning the protocol for a placebo chiropractic treatment in the randomized clinical trial for which it was designed.

Factors affecting use of chiropractic services in seven midwestern states of the United State.

Although chiropractic is used by approximately 10 percent of the U.S. population, predictors of its use have not been definitively described. Previous studies have suggested that chiropractic users differ from nonusers in a number of sociodemographic characteristics, but their findings are inconsistent, perhaps because of differences in populations sampled and dates of data collection, most of which are prior to 1990. Regional studies have been conducted in rural areas based on the premise that rural residents are more likely than non-rural residents to use chiropractice; however, this premise has not been definitively documented. The purpose of this study was to provide clarification of these sociodemographic predictors of chiropractic use in Illinois, Iowa, Minnesota, Missouri, Nebraska, South Dakota and Wisconsin by characterizing chiropractic users and nonusers in terms of sociodemographics, including rural or non-rural residence, and presence of low back pain. Data from 1,511 respondents to a 1994 population-based survey, conducted by the University of Iowa Social Science Institute, were analyzed. Unconditional logistic regression was used to derive odds ratios and 95 percent confidence intervals for univariate and multiple regression models. Overall, 15.1 percent of respondents had used chiropractic within the last year, most often for low back pain (57 percent). Chiropractic use was less likely in African Americans, Hispanics and Asians than whites, less likely by non-rural than rural residents, and less likely in Catholics than Protestants in states other than Iowa and South Dakota. Overall, 42.7 percent of workers with low back pain reported using chiropractic, and use increased with age but remained significantly related to race, rural or non-rural residence, state of residence and religious preference. Race, rural or non-rural residence, state of residence and religious preference, independently of low back pain, affect use of chiropractice in seven Midwestern states.

Spinal manipulative therapy versus a low force mimic maneuver for women with primary dysmenorrhea: a randomized, observer-blinded, clinical trial.

Non-drug therapies for women with primary dysmenorrhea are primarily based on anecdotal evidence and small-scale clinical studies. This randomized, observer-blinded, clinical trial evaluated the efficacy of spinal manipulative therapy (SMT) in the treatment of women with primary dysmenorrhea. Women were recruited from the Chicago metropolitan area and evaluated for inclusion through four screening levels. One hundred thirty eight women, ages 18-45, with primary dysmenorrhea diagnosed by participating gynecologists, were randomly assigned to either SMT or a low-force mimic (LFM) maneuver. No treatment occurred at menstrual cycle 1. Treatment for both groups took place on day 1 of cycles 2, 3 and 4, and prophylactic treatment of three visits took place during the 7 days before cycles 3 and 4. Main outcome measures were the Visual Analog Scale (VAS) and plasma concentration of the prostaglandin F2alpha metabolite, 15-keto-13,14-dihydro-prostaglandin F2alpha (KDPGF2alpha), measured 15 min before treatment and 60 min after treatment on day 1 of four consecutive menstrual cycles. The Moos' Menstrual Distress Questionnaire (MDQ) was also administered after treatment on day 1 of each cycle. At cycle 2, the post-treatment VAS scores decreased for both groups, with no statistically significant difference in pre- to post-treatment scores between the two groups (P = 0.44). The changes in pre- to post-treatment KDPGF2alpha levels were not statistically different between the SMT and LFM groups (P = 0.15). No treatment effects were detected over the three cycles for VAS, KDPGF2alpha or MDQ (P = 0.65, P = 0.61 and P = 0.78, respectively). However, there were statistically significant linear time effects for VAS (P = 0.008), MDQ (P < 0.001), and borderline significance for KDPGF2alpha (P = 0.054); these decreases were not considered clinically meaningful. The LFM maneuver used in this study was designed to act as a 'placebo-like' control treatment in comparison with SMT. Although it is possible that the trial did not continue long enough for any placebo effect of the LFM to wash out, it seems more likely that this maneuver was indistinguishable from SMT. Therefore, the postulated superior benefit of high-velocity, short-lever, low-amplitude, high-force spinal manipulation to a low-force maneuver is not supported by the results of this study. 1999 International Association for the Study of Pain.

Use of complementary healthcare practices among chiropractors in the United States: a survey.

CONTEXT: Although chiropractic is the most commonly used complementary healthcare practice, chiropractors have not been surveyed in depth about their attitudes toward and practice of complementary and alternative therapies apart from spinal manipulation. OBJECTIVES: To examine attitudes among US chiropractors on the role of their profession in complementary healthcare and to gather data on the types of complementary healthcare practices chiropractors use. DESIGN: Descriptive, cross-sectional study using a mail-in survey. SETTING: United States. PARTICIPANTS: Random sample of US chiropractors stratified by zip code region. RESULTS: A total of 563 surveys were completed, for a response rate of 30%. Respondents were almost equally divided on their responses to the question "Do you feel that chiropractic should at the present time be termed 'complementary'?" Although many respondents (68%) believed that chiropractic was viewed as a therapeutic modality, more (82%) believed that it should be viewed as a complete system. The therapies most commonly used by respondents in their practice were acupressure (72%), massage (72%), mineral supplements (63%), and herbs (56%). CONCLUSION: The disparity between the established view of chiropractic as synonymous with spinal manipulation and the profession's view of chiropractic as a complete system indicates a need for better interprofessional communication.