Risk factors for musculoskeletal-related occupational disability among US Army soldiers.

INTRODUCTION: Minimising temporary and permanent disability associated with musculoskeletal conditions (MSK-D) is critical to the mission of the US Army. Prior research has identified potentially actionable risk factors for overall military disability and its MSK-D subset, including elevated body mass index, tobacco use and physical fitness. However, prior work does not appear to have addressed the impact of these factors on MSK-D when controlling for a full range of factors that may affect health behaviours, including aptitude scores that may serve as a proxy for health literacy. Identifying risk factors for MSK-D when providing control for all such factors may inform efforts to improve military readiness. METHODS: We studied 494 757 enlisted Army soldiers from 2014 to 2017 using a combined medical and administrative database. Leveraging data from the Army's digital 'eProfile' system of duty restriction records, we defined MSK-D as the first restriction associated with musculoskeletal conditions and resulting in the inability to deploy or train. We used multivariable Cox proportional hazards regression to assess the associations between incident MSK-D and selected risk factors including aptitude scores, physical fitness test scores, body mass index and tobacco use. RESULTS: Among the subjects, 281 278 (45.14%) experienced MSK-D. In the MSK-D hazards model, the highest effect size was for failing the physical fitness test (adjusted HR=1.63, 95% CI 1.58 to 1.67, p<0.001) compared with scoring ≥290 points. CONCLUSIONS: The analysis revealed the strongest associations between physical fitness and MSK-D. Additional efforts are warranted to determine potential mechanisms for the observed associations between selected factors and MSK-D.

An ecological risk assessment of the acute and chronic effects of the herbicide clopyralid to rainbow trout (Oncorhynchus mykiss).

Clopyralid (3,6-dichloro-2-pyridinecarboxylic acid) is a pyridine herbicide frequently used to control invasive, noxious weeds in the northwestern United States. Clopyralid exhibits low acute toxicity to fish, including the rainbow trout (Oncorhynchus mykiss) and the threatened bull trout (Salvelinus confluentus). However, there are no published chronic toxicity data for clopyralid and fish that can be used in ecological risk assessments. We conducted 30-day chronic toxicity studies with juvenile rainbow trout exposed to the acid form of clopyralid. The 30-day maximum acceptable toxicant concentration (MATC) for growth, calculated as the geometric mean of the no observable effect concentration (68 mg/L) and the lowest observable effect concentration (136 mg/L), was 96 mg/L. No mortality was measured at the highest chronic concentration tested (273 mg/L). The acute:chronic ratio, calculated by dividing the previously published 96-h acutely lethal concentration (96-h ALC(50); 700 mg/L) by the MATC was 7.3. Toxicity values were compared to a four-tiered exposure assessment profile assuming an application rate of 1.12 kg/ha. The Tier 1 exposure estimation, based on direct overspray of a 2-m deep pond, was 0.055 mg/L. The Tier 2 maximum exposure estimate, based on the Generic Exposure Estimate Concentration model (GEENEC), was 0.057 mg/L. The Tier 3 maximum exposure estimate, based on previously published results of the Groundwater Loading Effects of Agricultural Management Systems model (GLEAMS), was 0.073 mg/L. The Tier 4 exposure estimate, based on published edge-of-field monitoring data, was estimated at 0.008 mg/L. Comparison of toxicity data to estimated environmental concentrations of clopyralid indicates that the safety factor for rainbow trout exposed to clopyralid at labeled use rates exceeds 1000. Therefore, the herbicide presents little to no risk to rainbow trout or other salmonids such as the threatened bull trout.

An ecological risk assessment of the exposure and effects of 2,4-D acid to rainbow trout (Onchorhyncus mykiss).

Numerous state and federal agencies are increasingly concerned with the rapid expansion of invasive, noxious weeds across the United States. Herbicides are frequently applied as weed control measures in forest and rangeland ecosystems that frequently overlap with critical habitats of threatened and endangered fish species. However, there is little published chronic toxicity data for herbicides and fish that can be used to assess ecological risk of herbicides in aquatic environments. We conducted 96-h flowthrough acute and 30-day chronic toxicity studies with swim-up larvae and juvenile rainbow trout (Onchorhyncus mykiss) exposed to the free acid form of 2,4-D. Juvenile rainbow trout were acutely sensitive to 2,4-D acid equivalent at 494 mg/L (95% confidence interval [CI] 334-668 mg/L; 96-h ALC(50)). Accelerated life-testing procedures, used to estimate chronic mortality from acute data, predicted that a 30-day exposure of juvenile rainbow trout to 2,4-D would result in 1% and 10% mortality at 260 and 343 mg/L, respectively. Swim-up larvae were chronically more sensitive than juveniles using growth as the measurement end point. The 30-day lowest observable effect concentration (LOEC) of 2,4-D on growth of swim-up larvae was 108 mg/L, whereas the 30-day no observable effect concentration (NOEC) was 54 mg/L. The 30-day maximum acceptable toxicant concentration (MATC) of 2,4-D for rainbow trout, determined as the geometric mean of the NOEC and the LOEC, was 76 mg/L. The acute:chronic ratio was 6.5 (i.e., 494/76). We observed no chronic effects on growth of juvenile rainbow trout at the highest concentration tested (108 mg/L). Worst-case aquatic exposures to 2,4-D (4 mg/L) occur when the herbicide is directly applied to aquatic ecosystems for aquatic weed control and resulted in a 30-day safety factor of 19 based on the MATC for growth (i.e., 76/4). Highest nontarget aquatic exposures to 2,4-D applied following terrestrial use is calculated at 0.136 mg/L and resulted in a 30-day safety factor of 559 (e.g., 76/0.163). Assessment of the exposure and response data presented herein indicates that use of 2,4-D acid for invasive weed control in aquatic and terrestrial habitats poses no substantial risk to growth or survival of rainbow trout or other salmonids, including the threatened bull trout (Salvelinus confluentus).

An ecological risk assessment of the acute and chronic toxicity of the herbicide picloram to the threatened bull trout (Salvelinus confluentus) and the rainbow trout (Onchorhyncus mykiss).

We conducted acute and chronic toxicity studies of the effects of picloram acid on the threatened bull trout (Salvelinus confluentus) and the standard coldwater surrogate rainbow trout (Oncorhynchus mykiss). Juvenile fish were chronically exposed for 30 days in a proportional flow-through diluter to measured concentrations of 0, 0.30, 0.60, 1.18, 2.37, and 4.75 mg/L picloram. No mortality of either species was observed at the highest concentration. Bull trout were twofold more sensitive to picloram (30-day maximum acceptable toxic concentration of 0.80 mg/L) compared to rainbow trout (30-day maximum acceptable toxic concentration of 1.67 mg/L) based on the endpoint of growth. Picloram was acutely toxic to rainbow trout at 36 mg/L (96-h ALC50). The acute:chronic ratio for rainbow trout exposed to picloram was 22. The chronic toxicity of picloram was compared to modeled and measured environmental exposure concentrations (EECs) using a four-tiered system. The Tier 1, worst-case exposure estimate, based on a direct application of the current maximum use rate (1.1 kg/ha picloram) to a standardized aquatic ecosystem (water body of 1-ha area and 1-m depth), resulted in an EEC of 0.73 mg/L picloram and chronic risk quotients of 0.91 and 0.44 for bull trout and rainbow trout, respectively. Higher-tiered exposure estimates reduced chronic risk quotients 10-fold. Results of this study indicate that picloram, if properly applied according to the manufacturer's label, poses little risk to the threatened bull trout or rainbow trout in northwestern rangeland environments on either an acute or a chronic basis.

Characterization of productive and sterile transcripts from the immunoglobulin heavy-chain locus: processing of micron and muS mRNA.

An analysis of the sizes and sequence content of nuclear RNA transcripts of the heavy-chain locus in two B-cell lymphomas, 70Z/3 and 38C-13, and in selected hybridoma derivatives of 38C has led to the identification of two distinct precursors of the mRNAs encoding the membrane and secretory forms of mu chain. These precursors, termed Pm1 and Ps1, extend from a common 5' terminus (presumably the cap site) to alternative polyadenylation sites located 3' of the membrane and secretory tailpieces, Pm1 and Ps1 are present in similar amounts in lymphomas, indicating roughly equivalent usage of the two polyadenylation sites, whereas Ps1 much greater than Pm1 in hybridomas, indicating that mature plasma cells produce a trans-acting factor which enhances cleavage at the proximal (muS) site. The lymphomas also synthesize several nonproductive or sterile mu (Smu) transcripts from the second H allele. One class of sterile mu transcripts appears to be initiated about 1 kilobase downstream from the JH4 element. In 70Z, in which the nonproductive H allele has undergone a D1J2 fusion, another initiation site was located about 0.3 kilobase upstream of the D1 element. The sterile mu transcripts exhibit the same regulated termination at alternative polyadenylation sites as the mu mRNA precursors, although their rate of production is not necessarily coupled to that of the productive allele. This analysis has also defined probable processing pathways for productive and sterile components in which there is a 5' leads to 3' order for the excision of the large introns.

Nonproductive kappa immunoglobulin genes: recombinational abnormalities and other lesions affecting transcription, RNA processing, turnover, and translation.

Six nonproductive kappa immunoglobulin genes (kappa- alleles) were cloned and sequenced. The structural abnormalities discerned from sequence analysis were correlated with functional lesions at the level of transcription, RNA processing, turnover, and translation. Four kappa- alleles, three containing V kappa genes and one not, are transcribed at normal or even greater than normal rates, the defects in these genes being expressed at various posttranscriptional levels. The other two kappa- alleles, both of which lacked V genes, exhibited greatly depressed yet clearly detectable transcriptional activity. These results are consistent with a hierarchical relationship between enhancer and promoter elements in which the enhancer establishes transcriptional competence at the kappa locus and the promoter (or pseudopromoter) determines the relative level of transcriptional activity. One of the structural abnormalities discovered in this study, a large deletion which removes the entire J kappa region, also provides new insight into the mechanism of VJ and VDJ recombination.

Ectopic pregnancy subsequent to sterilization: histologic evaluation and clinical implications.

Ten ectopic pregnancies subsequent to tubal sterilization were histologically evaluated. In seven of the ten cases, the sites for the ectopic implantation appeared to be related to the presence of a distal remaining tubal segment that had a tuboperitoneal fistula on the medial side. As against a currently held opinion that the ectopic implantation occurs secondary to a relative disparity in the size of the sperm, the fertilized ovum, and the proximal tuboperitoneal fistula, we believe that the implantations are influenced by probable fluid movements within the remaining tubal segments. The need to consider conservative surgical approaches and good intraoperative notations in patients with an ectopic pregnancy subsequent to sterilization is stressed.

Neurotensin stimulates neutrophil adherence to bronchial epithelial cells in vitro.

Neutrophils and neuropeptides have both been implicated in airway inflammation. We hypothesized that neurotensin, a neuropeptide found in the airways, would stimulate neutrophil adherence to bronchial epithelial cells. Adherence was assessed using 51Cr-labelled human neutrophils added to confluent monolayers of bovine bronchial epithelial cells. Neurotensin added to bronchial epithelial cells produced a time-and concentration-dependent increase in adherence which was maximal at 4 h and 10(-10)M (17.6 +/- 1.4% vs. 6.1 +/- 0.4%, p < 0.01). Conversely, neurotensin stimulation of neutrophils induced a concentration-dependent and rapid ( < 5 min) increase in adherence which was also maximal at 10(-10)M (27.1 +/- 1.9% vs. 10.1 +/- 1.4%, p < 0.01). The effects were reproduced by the carboxy portion of the molecule. Anti-CD11a, -CD11b or -ICAM-1 antibodies significantly decreased the neurotensin-induced increase in adherence. These data suggest an important role for neurotensin in modulating airway inflammation.

Bovine bronchial epithelial cells metabolize L-arginine to L-citrulline: possible role of nitric oxide synthase.

The conversion of L-arginine to L-citrulline is catalyzed by nitric oxide synthase (NOS), and results in the release of nitric oxide (NO). We hypothesized that bronchial epithelial cells metabolize L-arginine to L-citrulline. We found that cell lysates obtained from unstimulated, cultured bovine bronchial epithelial cells (BBECs) converted L-[3H]arginine to L-[3H]citrulline. This conversion was attenuated by three competitive NOS inhibitors and modulated by lipopolysaccharide and cigarette smoke extract (p < 0.01, all comparisons). These data demonstrate that BBECs metabolize L-arginine to L-citrulline and implicate a role for the L-arginine:NOS biosynthetic pathway in modulating airway responses.

Inducible transcription of the unrearranged kappa constant region locus is a common feature of pre-B cells and does not require DNA or protein synthesis.

Transcription of unrearranged kappa constant region (kappa 0) loci is dramatically induced in pre-B cells transformed by the Abelson murine leukemia virus when the cells are exposed to bacterial lipopolysaccharide (LPS). Transcriptional activity, detected both by accumulation of the 8-kilobase kappa 0 RNA product and by nuclear run-on measurements, is evident within a few hours after exposure to LPS and continues to increase over a 24-hr period. During this time, transcription of rearranged mu heavy-chain loci remains at the basal constitutive level. In accord with previous studies of the B-cell lymphoma 70Z/3, this transcriptional activation is accompanied by the appearance of a DNase I-hypersensitive site in the kappa enhancer region but not by any detectable hypomethylation of the locus. Moreover, the present studies demonstrate that induction of kappa transcription can occur in the absence of DNA or protein synthesis. These results have led us to propose a model in which an external signal such as LPS or a functionally equivalent lymphokine may initiate kappa transcription in pre-B cells by modifying or overriding the activity of an enhancer-specific factor.

Lipopolysaccharide-induced transcription of the kappa immunoglobulin locus occurs on both alleles and is independent of methylation status.

The transcriptional activity of the kappa immunoglobulin genes in a B-cell lymphoma line, 7OZ/3 was measured before and after stimulation by lipopolysaccharide (LPS). Analyses of accumulated nuclear RNA components and of nascent transcripts showed that LPS induces transcription of both the productively rearranged (kappa+) and the unrearranged (kappa) allele in these cells. This pattern of transcriptional activation correlates well with the LPS induced appearance of a DNAase I hypersensitive site on both alleles in the vicinity of a putative enhancer element (Parslow and Granner, Nucl. Acids Res. 11, 4775, 1983). However, the transcriptional activation is not accompanied by detectable hypomethylation at Hha I and Hpa II sites which are normally undermethylated when kappa genes are constitutively expressed. These findings have enabled us to evaluate the relative importance of various structural parameters to the transcriptional competence of the kappa locus.

A cell culture assay for tumor-promoter-dependent progression toward neoplastic phenotype: detection of tumor promoters and promotion inhibitors.

Mouse epidermal cell lines have been identified which respond to tumor-promoting (but not nonpromoting) phorbol esters with an irreversible shift in anchorage independence, an in vitro marker of neoplastic phenotype. This response may be analogous to a later stage of tumor promotion in vivo. The shift occurs at TPA concentrations as low as 0.1 ng/ml (1.6 x 10(-10) M). The specificity of the soft agar growth response is not limited to phorbol esters but extends to nonphorbol plant diterpenes such as mezerein, to detergents, to polycyclic hydrocarbons present in cigarette smoke, and to some growth factors. All of the above classes of compounds have been previously shown to have tumor-promoting and/or cocarcinogenic activity in mouse skin in vivo. Clonal heterogeneity for TPA responsiveness has been found. Clones which were highly responsive to phorbol esters were also highly responsive to other classes of promoters, indicating their usefulness both for promoter detection and mechanism studies. The anchorage-independence to response to TPA was inhibited by a series of retinoids whose activity paralleled that for inhibiting tumor promotion in vivo. Both retinoid inhibition and clonal heterogeneity for promoter response are being utilized to study determinants of preneoplastic progression.

Recognition of synthetic speech by hearing-impaired elderly listeners.

The Modified Rhyme Test (MRT), recorded using natural speech and two forms of synthetic speech, DECtalk and Votrax, was used to measure both open-set and closed-set speech-recognition performance. Performance of hearing-impaired elderly listeners was compared to two groups of young normal-hearing adults, one listening in quiet, and the other listening in a background of spectrally shaped noise designed to simulate the peripheral hearing loss of the elderly. Votrax synthetic speech yielded significant decrements in speech recognition compared to either natural or DECtalk synthetic speech for all three subject groups. There were no differences in performance between natural speech and DECtalk speech for the elderly hearing-impaired listeners or the young listeners with simulated hearing loss. The normal-hearing young adults listening in quiet out-performed both of the other groups, but there were no differences in performance between the young listeners with simulated hearing loss and the elderly hearing-impaired listeners. When the closed-set identification of synthetic speech was compared to its open-set recognition, the hearing-impaired elderly gained as much from the reduction in stimulus/response uncertainty as the two younger groups. Finally, among the elderly hearing-impaired listeners, speech-recognition performance was correlated negatively with hearing sensitivity, but scores were correlated positively among the different talker conditions. Those listeners with the greatest hearing loss had the most difficulty understanding speech and those having the most trouble understanding natural speech also had the greatest difficulty with synthetic speech.

Intraoperative antibiotic irrigation as prophylaxis in abdominal hysterectomy: a preliminary report.

A preliminary report regarding the use of an intraoperative, intraperitoneal antibiotic solution in patients having transabdominal hysterectomy reveals that the postoperative morbidity assessed by the diagnosis of cuff cellulitis or pelvic abscess was 4.7%. This morbidity represents a substantial reduction in the incidence of cuff cellulitis (27.0%) noted in a comparison group of 367 patients having abdominal hysterectomy at our institution during a two-year period. These preliminary data strongly suggest that antibiotic solutions given intraperitoneally at the time of abdominal hysterectomy reduce morbidity due to cuff cellulitis.

Complement activation by cigarette smoke.

Lung disease secondary to cigarette smoking is associated with an influx of neutrophils and monocytes into the lower respiratory tract. To determine whether cigarette smoke can generate chemotactic activity, human serum was exposed to cigarette smoke and evaluated for neutrophil and monocyte chemotactic activity. Serum exposed to cigarette smoke attracted significantly greater numbers of neutrophils and monocytes compared with normal human serum exposed to air (P less than 0.01, both comparisons). The increase in chemotactic activity was partially attenuated by EDTA but not by ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) and MgCl2 (P greater than 0.05, both comparisons), suggesting activation of the alternate complement pathway. To evaluate the capacity of cigarette smoke to activate the complement system, smoke-exposed serum was evaluated for cleavage of properdin factor B and C3 using immunoelectrophoresis and for C5a using a radioimmunoassay. Cleavage of properdin factor B and C3 was observed in the smoke-exposed serum and C5a was detected in the smoke-exposed serum (112 +/- 31 ng/ml). These data suggest that complement activation may play a role in directing the influx of neutrophils and monocytes into the lungs of cigarette smokers.

Mode of regulation of immunoglobulin mu- and delta-chain expression varies during B-lymphocyte maturation.

The transcription, processing, and accumulation of mu and delta mRNA was studied in several cell lines representing different stages of B-lymphocyte maturation. Our results indicate that the relative content of mu and delta mRNA is the major determinant of the IgM versus IgM + IgD phenotype and that the production of delta mRNA is regulated at distinctly different levels of gene expression in early and later developmental stages. In B cell lymphomas typical of early stages, transcription extends over the entire 25 kb of the mu- delta locus and the relative content of mu and delta mRNA is determined at the level of mRNA processing. In contrast, in cells typical of mature IgM secretors, transcription is terminated abruptly between the mu and delta genes, precluding the production of delta mRNA. We propose a model that accounts for qualitative and quantitative changes in mu-delta expression in the developing B lymphocyte.

Comparison of once daily doses of lansoprazole (15, 30, and 60 mg) and placebo in patients with gastric ulcer.

OBJECTIVES: A multicenter, double-blind study was conducted in 268 patients to compare the safety and efficacy of 15, 30, and 60 mg of lansoprazole and placebo in the treatment of gastric ulcer. METHODS: The study included an 8-wk treatment period to assess healing and a 6-month posttreatment period to evaluate ulcer recurrence. Endoscopies were performed, GI symptoms and antacid use were assessed, and safety evaluations were conducted, including serum gastrin and biopsies of the lesions and the greater curvature of the stomach. RESULTS: At week 4, healing rates were significantly higher with lansoprazole 15 and 30 mg (64.6 and 58.1%, respectively) compared with placebo (37.5%). By week 8, healing rates were 76.7% with placebo, 92.2% with 15 mg of lansoprazole, 96.8% with 30 mg, and 93.2% with 60 mg of lansoprazole (p < 0.05). The drug was well tolerated, with no significant differences from placebo in the incidence of adverse events. Fasting serum gastrin increased in all lansoprazole groups, reaching a plateau by week 2 and returning to baseline levels by month 1 posttreatment. No significant increase in Grimelius-positive cells or inflammation was evident. All but two patients had normal gastric morphology evaluated by Solcia classification. CONCLUSIONS: Lansoprazole, 15, 30, and 60 mg, administered once daily before eating, healed gastric ulcers to an approximately equal degree, and all were significantly better than placebo.

Effects of age on serial recall of natural and synthetic speech.

The present study addressed the effects of aging on auditory serial-recall performance for natural and synthetic words. Word difficulty, measured in terms of frequency of occurrence and phonological similarity, and rate of presentation were also manipulated in an effort to determine which processes underlying serial-recall performance, if any, were affected by aging. Results indicated that age per se had little effect on short-term (working) memory as measured by the serial recall of monosyllabic words. Rate of presentation had little effect on recall for either subject group. Word difficulty, on the other hand, affected recall for both groups, with easy words being more readily recalled than hard words.