Lateral Patellar Inclination Angle Measured via a Two-Image Technique on Axial Magnetic Resonance Imaging.

Lateral patellar inclination (LPI) measures patellar tilt and is historically described on axial X-ray or a single magnetic resonance image (MRI). Given the variability in patellar height, LPI may be better represented by performing this measurement on two separate axial MRI images. We hypothesized that a two-image LPI measurement would be different from the current single-image LPI and have similar, if not superior reliability. Sixty-five patients treated for patellar instability (PI) between 2014 and 2017 were identified. Single image and two-image LPI were measured on axial MRI images. All measurements were performed by two independent observers. Reliability analysis was based on three observers' measurements of 30 randomly selected patients. Both the one image and two image LPI showed good inter-rater reliability (intraclass correlation coefficient [ICC] = 0.71 and 0.89, respectively), although the two image LPI had less variability. Both single image and two image LPI had near perfect intra-rater reliability (ICC = 0.98 and 0.98, respectively). Average single image LPI (14.6 ± 9.9 degrees) was 6.1 ± 3.4 degrees less than the average two image LPI (19.6 ± 9.4 degrees) (p = 0.037). Referencing a previously described 13.5 degrees maximum threshold, 54% of the patients had excessive patellar tilt based on single image LPI, while 73% had pathologic patellar tilt based on two image LPI. Two image LPI has similar reliability with less inter-rater variability compared with the historical single image LPI measurement. Significantly greater patellar tilt was identified with two image LPI that was found with single image LPI. A larger percentage of patients were classified as having pathologic patellar tilt based on two image LPI than single image LPI. The two image LPI provides more consistent and representative measurements of patellar tilt. Previously described threshold values for patellar tilt should be re-examined using this new measurement technique to appropriately risk stratify patients with PI and patellofemoral pain.

Functionalization of gold nanoparticles by ß-cyclodextrin as a probe for the detection of heavy metals in water and photocatalytic degradation of textile dye.

Gold nanoparticles (AuNPs) and AuNPs functionalized by ß-cyclodextrin (ß-CD/AuNPs) were prepared successfully through chemical reduction method. The structural, morphological, optical, compositional and vibrational studies for the AuNPs and ß-CD/AuNPs were carried out. Functionalization of AuNPs by ß-CD was confirmed with FT-IR results. The UV-visible absorption spectra exhibit a red-shift with decreasing average particle size. This sustains the enhancement in surface area (SA) to volume (V) ratio that is one of the peculiar characteristics of nanoparticles. TEM results show that ß-CD/AuNPs formed were monodispersed and self assembled. Also it shows a decrease in average particle size and improved distribution. The use of ß-CD in the synthesis of AuNPs are revealed not only create uniform small sized nanoparticles but these water soluble nanoparticles have very good antibacterial action by inhibiting the growth of bacteria commonly found in water and sensing activity for sensing the concentration of toxic metals in water. The sensitivity of the system towards copper (Cu) concentration was found as 1.788/mM for ß-CD/AuNPs and 1.333/mM for AuNPs. The photocatalytic action of the obtained nanoparticles increases with decreasing average particle size. The kapp value of this photocatalytic degradation of textile dyeing waste water in presence of AuNPs was 0.002/min and ß-CD/AuNPs was 0.005/min. This is a non-toxic and eco-friendly approach.

Lateral Trochlear Inclination Angle: Measurement via a 2-Image Technique to Reliably Characterize and Quantify Trochlear Dysplasia.

BACKGROUND: Trochlear dysplasia (TD) is a risk factor for patellar instability (PI). The Dejour classification categorizes TD but has suboptimal reliability. Lateral trochlear inclination (LTI) is a quantitative measurement of trochlear dysplasia on a single axial magnetic resonance imaging (MRI) scan. HYPOTHESIS: A modified LTI measurement technique using 2 different axial MRI scans that reference the most proximal aspect of the trochlear cartilage on 1 image and the fully formed posterior condyles on the second image would be as reliable as and significantly different from the single-image measurement technique for LTI. Further, the 2-image LTI would adequately represent overall proximal trochlear morphologic characteristics. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 2. METHODS: Patients aged 9 to 18 years treated for PI between 2014 and 2017 were identified. The Dejour classification was radiographically determined. Single-image LTI was measured on a single axial MRI scan at the most proximal aspect of visible trochlear cartilage. A 2-image LTI was measured from 2 separate MRI scans: 1 at the most proximal aspect of trochlear cartilage and the second at the fully formed posterior condyles. This 2-image LTI was repeated at 3 subsequent levels (the first measurement is referred to as LTI-1; repeated measurements are LTI-2, LTI-3, and LTI-4, moving distally). In total, 65 patients met the inclusion criteria, and 30 were randomly selected for reliability analysis. RESULTS: Inter- and intrarater reliability trended toward more variability for single-image LTI (intraclass correlation coefficient [ICC], 0.86 and 0.88, respectively) than for 2-image LTI (ICC, 0.97 and 0.96, respectively). The Dejour classification had lower intra- and interrater reliability (ICC, 0.31 and 0.73, respectively). Average single-image LTI (9.2° ± 12.6°) was greater than average 2-image LTI-1 (4.2° SD ± 11.9°) (P = .0125). Single-image LTI classified 60% of patients with PI as having TD, whereas the 2-image LTI classified 71% as having TD. The 2-image LTI was able to capture 91% of overall proximal trochlear morphologic characteristics. CONCLUSION: LTI has higher reliability when performed using a 2-image measurement technique compared with single-image LTI and Dejour classification. The strong correlation between 2-image LTI and average LTI shows that 91% of TD is represented on the most proximal axial image. Because the single-image measurement appears to underestimate dysplasia, previously described thresholds should be reexamined using this 2-image technique to appropriately characterize TD.

Effect of Trochlear Dysplasia on Commonly Used Radiographic Parameters to Assess Patellar Instability.

BACKGROUND: Trochlear dysplasia (TD) is an important anatomic risk factor for patellar instability (PI). Several imaging-based risk factors for PI have been established, but it is unclear what effect TD has on these measurements, and the Dejour method of categorizing TD has been shown to be unreliable. The lateral trochlear inclination (LTI) is a quantifiable measurement of proximal trochlear morphology. Recently, a modified technique for measuring LTI referencing the posterior condylar angle has demonstrated near-perfect reliability and may serve as a new standard for quantifying TD. PURPOSE/HYPOTHESIS: The purpose of this study was to evaluate how TD, expressed in terms of LTI, affects historically used measures of PI, including the sulcus angle (SA), tibial tuberosity to trochlear groove (TT-TG) distance, lateral patellar inclination (LPI), and Caton-Deschamps (CD) ratio. We hypothesized that lower LTI (ie, more dysplastic trochlea) will correlate with higher SA and TT-TG distances, increased patellar tilt, and more patella alta. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Patients aged 9 to 18 years treated for PI between January 2014 and August 2017 were queried. On magnetic resonance imaging (MRI), LTI, SA, LPI, and the TT-TG measured at the most proximal (pTT-TG) and distal (dTT-TG) aspects of the fully formed trochlear groove were measured on axial images. CD ratio was measured using sagittal MRI as well as lateral radiographs. All measurements were performed by 2 independent observers. Patients were included if there was a diagnosis of PI that was confirmed with a chart review and if there were appropriate imaging studies to analyze. RESULTS: A total of 65 patients met inclusion criteria for this study. Average pTT-TG distance (15.7 ± 4.5 mm) was not significantly different from dTT-TG distance (15.7 ± 4.2 mm) (P = .94). LTI had a weak but significant inverse correlation with pTT-TG (r = -0.40; ß = -0.15 mm; P < .001) and SA (r = -0.43; ß = -0.478°; P < .001). There was a moderate and significant inverse correlation of LTI with dTT-TG (r = -0.593; ß = -0.21 mm; P < .001) and with LPI (r = -0.69; ß = -0.54°; P < .001). There was a weak but significant correlation between LTI and the MRI-based CD ratio (r = 0.279; ß = 0.149; P = .005). Radiograph-based CD ratio did not show a significant correlation with LTI (r = -0.189; P = .135). CONCLUSION: Smaller (ie, more dysplastic) LTI values correlated significantly with larger TT-TG, SA, LPI, and MRI-based CD ratio measurements. The relationship between SA and LTI is intuitive, but the relationship between LTI and the other analyzed variables suggests that they are dependent variables to TD and may not be consistent independent risk factors for PI. Together, these suggest that TD alters the radiographic interpretation of TT-TG and patellar tilt. The correlation between TD and patellar height is unclear and warrants further investigation.

Medial Quadriceps Tendon Femoral Ligament Reconstruction Technique and Surgical Anatomy.

Medial patellofemoral ligament reconstruction risks patellar fracture with the osseous violation necessary for patellar attachment. Anatomic studies identify an entire medial patellofemoral complex of structures responsible for medial restraint to patellar lateral instability. One specific component of this complex is the medial quadriceps tendon femoral ligament (MQTFL). This note presents the technique, pearls and pitfalls, and critical surgical anatomy necessary for successful MQTFL reconstruction-a treatment strategy for patellar instability with no increased risk for patellar fracture. An autograft hamstring tendon or allograft tendon is fixed to the anatomically identified femoral origin and passed deep to the vastus medialis obliquus to then weave around the distal medial quadriceps tendon. This simulates the native anatomic interdigitation of the MQTFL with the quadriceps tendon and provides a stable restraint to prevent lateral patellar subluxation or dislocation.

Treatment of ACL Tears in the Skeletally Immature Patient.

The understanding and treatment of anterior cruciate ligament tears in skeletally immature patients continues to evolve. While conservative management was a mainstay of treatment, poor outcomes have led to several surgical techniques aimed at stabilizing the knee, optimizing outcome, and minimizing the chance of growth disturbance. Current techniques have, in large part, accomplished these goals but challenges remain. Looking to the future, different graft options, primary repair techniques, and rigorous prospective studies will help improve outcomes for this challenging patient population.

Arthroscopic Viewing Position Affects Anterior Cruciate Ligament Reconstruction Femoral Tunnel Length Measurements.

PURPOSE: To purpose of this study was to compare arthroscopic anterior cruciate ligament (ACL) reconstruction femoral tunnel length measurements from the anterolateral portal between the standard notch view using a 30° arthroscope versus a "top-down" view utilizing a 70° arthroscope to visual the far side of the femoral tunnel aperture. METHODS: Arthroscopic femoral tunnel length measurements using calibrated reamers from the standard notch versus the "top-down" view were obtained and reviewed in 54 skeletally mature patients undergoing ACL reconstruction with no prior bony knee surgery. Patient age, height, weight, sex, and surgery laterality were also recorded. Measurements of femoral tunnel length were repeated using both views for inter-observer and intra-observer correlation. RESULTS: Inter-observer and intra-observer intra-class correlation coefficients for the standard notch view and "top-down" views were excellent, with higher reliability values appreciated using the "top down" view. Mean overall femoral tunnel length measurements obtained using the standard notch view were significantly longer than measurements from the "top-down" view (p < 0.001). CONCLUSIONS: The standard notch view provides significantly longer femoral tunnel length measurements in comparison to the "top-down" view.

Review of Testudobracon Quicke (Hymenoptera: Braconidae) with descriptions of four new species from south India.

The Braconinae is a generically diverse subfamily of Braconidae. The Old World genus Testudobracon Quicke is reviewed and four new species viz., T. athashi Ranjith sp. nov., T. malabaricus Sheeba sp. nov., T. shameeri Ranjith sp. nov. and T. travencorensis Sheeba sp. nov., are described from south India. A check list and key to the world species are provided.

Cost Analysis of Hemiarthroplasty Versus Reverse Shoulder Arthroplasty for Fractures.

Complex proximal humerus fractures in older patients can be treated with hemiarthroplasty (HA) or reverse shoulder arthroplasty (RSA), with both providing good pain relief and function. This study compared the costs, complications, and outcomes of HA vs RSA after proximal humerus fracture in older patients. Patients 65 years or older who were admitted between January 2007 and August 2011 with a 3- or 4-part proximal humerus fracture and treated with HA or RSA were identified. Surgeries were performed at the same institution by 1 of 3 surgeons trained in trauma or shoulder surgery. Operating room costs, implant costs, total costs to the patient and hospital, and range of motion were compared. In the study group, 8 patients (7 women and 1 man; mean age, 77 years) received HA and 16 patients (13 women and 3 men; mean age, 77 years) received RSA. Hemiarthroplasty implant cost and operating room cost were $9140 and $8900 less than those of RSA, respectively (P<.001). The total cost to the patient was $33,480 for HA vs $57,000 for RSA (P<.001) with no difference in admission length, transfusion requirements, or final range of motion. In patients with complex proximal humerus fractures, RSA restored function similar to HA and resulted in better pain and outcome scores. However, RSA had a significantly higher cost to both the patient and the hospital compared with HA. Further investigation of postsurgical rehabilitation costs, skilled nursing needs, or revision surgery will elucidate whether there is long-term functional or financial benefits to RSA over HA. [Orthopedics. 2016; 39(4):230-234.].

3-Benzoyl-1-(2-meth-oxy-phen-yl)thio-urea.

In the title compound, C15H14N2O2S, the central C2N2OS moiety is planar (r.m.s. deviation of fitted atoms = 0.0336 Å). This is ascribed to the formation of an S(6) loop stabilized by an intra-molecular N-H⋯O hydrogen bond; additional intramolecular N-H⋯O and C-H⋯S contacts are also noted. The dihedral angles between the central unit and the phenyl and benzene rings are 23.79 (7) and 29.52 (5)°, respectively. The thione S and ketone O atoms are mutually anti, as are the N-H H atoms; the O atoms lie to the same side of the mol-ecule. Centrosymmetric eight-membered {⋯HNC=S}2 synthons feature in the crystal packing. The resulting inversion dimers stack along the a axis and are connected into a three-dimensional structure by C-H⋯O and C-H⋯π inter-actions.

1-Benzoyl-3-(4-chloro-phen-yl)thio-urea dichloro-methane hemisolvate.

In the title hemisolvate, C14H11ClN2OS·0.5CH2Cl2, an anti disposition is found for the thione and ketone atoms, as well as the N-H H atoms; the dichloro-methane C atom lies on a twofold axis. The central chromophore (including the two adjacent ipso C atoms) is planar (r.m.s. deviation = 0.021 Å) owing to the presence of an intra-molecular N-H⋯O hydrogen bond, which closes an S(6) loop. Significant twists are evident in the mol-ecule, the dihedral angles between the central moiety and the phenyl and benzene rings being 29.52 (7) and 40.02 (7)°, respectively. In the crystal, eight-membered {⋯HNC= S}2 synthons with twofold symmetry form via N-H⋯S hydrogen bonds. The dimers are connected into a supra-molecular chain along [111] by C-H⋯O inter-actions. The chains stack along the c axis, forming columns which define channels in which the occluded dichloro-methane mol-ecules reside.

Effect of bar-code-assisted medication administration on nurses' activities in an intensive care unit: a time-motion study.

PURPOSE: The effect of bar-code-assisted medication administration (BCMA) on nurses' activities in an intensive care unit was evaluated. METHODS: A prospective, observational, time-motion study was conducted by considering two approaches to medication administration in an intensive care unit: paper-based medication administration (PBMA) and BCMA. The time spent on nursing activities was measured using a prevalidated time-motion observation instrument and categorized based on workflow factors such as direct patient care, indirect patient care, administration, and miscellaneous or other. A descriptive analysis was conducted with the amount of time spent on each of the nursing activities. A multivariate analysis of covariance was conducted to assess the difference between the two approaches for the amount of time spent on various categorized nursing activities. Covariates included in the analysis were patient characteristics, medication administration characteristics, and number of nurses involved in medication administration. RESULTS: A total of 101 PBMAs and 151 BCMAs were reviewed. The mean duration of total medication administration time was higher in the BCMA phase compared with the PBMA phase, as was the mean time spent on direct patient care activity. However, nurses spent less time on administration activity during BCMA. Statistical analysis revealed that the medication administration approach (BCMA versus PBMA) had a significant effect on time spent on direct patient care and medication administration activities. CONCLUSION: The implementation of BCMA led to a reduction in the time spent by nurses on medication administration activities and increased the time spent on direct patient care activities.

Descriptive analysis of workflow variables associated with barcode-based approach to medication administration.

Bedside barcode technology is used during medication administration to ensure patient safety. This study evaluated the workflow variables related to a bedside barcode technology-based medication administration process. A time-and-motion technique was used to assess the observational episodes related to medication administration conducted by registered nurses. In an observational episode, nurses spent adequate time in "documenting medications" and "giving medications." Nurses were primarily engaged in tasks at the patient's bedside.

Prioritizing research for trace pollutants and emerging contaminants in the freshwater environment.

Organic chemicals have been detected at trace concentrations in the freshwater environment for decades. Though the term trace pollutant indicates low concentrations normally in the nanogram or microgram per liter range, many of these pollutants can exceed an acceptable daily intake (ADI) for humans. Trace pollutants referred to as emerging contaminants (ECs) have recently been detected in the freshwater environment and may have adverse human health effects. Analytical techniques continue to improve; therefore, the number and frequency of detections of ECs are increasing. It is difficult for regulators to restrict use of pollutants that are a human health hazard; scientists to improve treatment techniques for higher priority pollutants; and the public to modify consumption patterns due to the vast number of ECs and the breadth of literature on the occurrence, use, and toxicity. Hence, this paper examines literature containing occurrence and toxicity data for three broad classes of trace pollutants and ECs (industrials, pesticides, and pharmaceuticals and personal care products (PPCPs)), and assesses the relevance of 71 individual compounds. The evaluation indicates that widely used industrials (BPF) and PPCPs (AHTN, HHCB, ibuprofen, and estriol) occur frequently in samples from the freshwater environment but toxicity data were not available; thus, it is important to establish their ADI. Other widely used industrials (BDE-47, BDE-99) and pesticides (benomyl, carbendazim, aldrin, endrin, ethion, malathion, biphenthrin, and cypermethrin) have established ADI values but occurrence in the freshwater environment was not well documented. The highest priority pollutants for regulation and treatment should include industrials (PFOA, PFOS and DEHP), pesticides (diazinon, methoxychlor, and dieldrin), and PPCPs (EE2, carbamazepine, ßE2, DEET, triclosan, acetaminophen, and E1) because they occur frequently in the freshwater environment and pose a human health hazard at environmental concentrations.

Molecular Characterization of Geographically Different Banana bunchy top virus Isolates in India.

Banana bunchy top disease (BBTD) caused by Banana bunchy top virus (BBTV) is one of the most devastating diseases of banana and poses a serious threat for cultivars like Hill Banana (Syn: Virupakshi) and Grand Naine in India. In this study, we have cloned and sequenced the complete genome comprised of six DNA components of BBTV infecting Hill Banana grown in lower Pulney hills, Tamil Nadu State, India. The complete genome sequence of this hill banana isolate showed high degree of similarity with the corresponding sequences of BBTV isolates originating from Lucknow, Uttar Pradesh State, India, and from Fiji, Egypt, Pakistan, and Australia. In addition, sixteen coat protein (CP) and thirteen replicase genes (Rep) sequences of BBTV isolates collected from different banana growing states of India were cloned and sequenced. The replicase sequences of 13 isolates showed high degree of similarity with that of South Pacific group of BBTV isolates. However, the CP gene of BBTV isolates from Shervroy and Kodaikanal hills of Tamil Nadu showed higher amino acid sequence variability compared to other isolates. Another hill banana isolate from Meghalaya state had 23 nucleotide substitutions in the CP gene but the amino acid sequence was conserved. This is the first report of the characterization of a complete genome of BBTV occurring in the high altitudes of India. Our study revealed that the Indian BBTV isolates with distinct geographical origins belongs to the South Pacific group, except Shervroy and Kodaikanal hill isolates which neither belong to the South Pacific nor the Asian group.

Cardiospermum halicacabum ethanol extract inhibits LPS induced COX-2, TNF-alpha and iNOS expression, which is mediated by NF-kappaB regulation, in RAW264.7 cells.

AIM OF THIS STUDY: Cardiospermum halicacabum L. is well known for its anti-inflammatory, analgesic and antipyretic activities. It has been used in Ayurveda and folk medicine for the treatment of rheumatism, fever and earache. But its mechanism of anti-inflammatory and analgesic action is still unclear, hence in this context, the objective of our study is to reveal the mechanism of anti-inflammatory and analgesic activity of Cardiospermum halicacabum L. which would form an additional proof to the traditional knowledge of Cardiospermum halicacabum L. MATERIALS AND METHODS: In this study the ethanolic extract of the whole plant was used to evaluate the anti-inflammatory action in mouse macrophage cell line RAW264.7 cells. The expression levels of cyclooxygenase (COX)-1, COX-2, tumor necrosis factor-alpha (TNF-alpha), inducible nitric oxide synthase (iNOS) and COX-2 protein expression by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot and nuclear factor kappa-B (NF-kappaB) binding activity by electrophoretic mobility shift assay (EMSA). RESULTS: We found that the ethanol extract dose dependently inhibit mRNA expression of COX-2, TNF-alpha, iNOS and COX-2 protein expression. But the extract did not affect the expression of COX-1 mRNA expression. Furthermore, Cardiospermum halicacabum L. ethanol extract inhibited the TNF-alpha induced DNA binding activity of NF-kappaB, which was associated with decreased p65 protein level in the nucleus in Jurkat cells. CONCLUSION: These results enabled to understand the mechanisms behind the anti-inflammatory and analgesic activity of Cardiospermum halicacabum L.

Fabrication and characterization of dye mixture doped polymer optical fiber as a broad wavelength optical amplifier.

Rhodamine 6G and Rhodamine B dye mixture doped polymer optical fiber amplifier (POFA), which can operate in a broad wavelength region (60 nm), has been successfully fabricated and tested. Tunable operation of the amplifier over a broad wavelength region is achieved by mixing different ratios of the dyes. The dye doped POFA is pumped axially using 532 nm, 10 ns laser pulses from a frequency doubled Q-switched Nd: YAG laser and the signals are taken from an optical parametric oscillator. A maximum gain of 22.3 dB at 617 nm wavelength has been obtained for a 7 cm long dye mixture doped POFA. The effects of pump energy and length of the fiber on the performance of the fiber amplifier are also studied. There exists an optimum length for which the amplifier gain is at a maximum value.

Side illumination fluorescence emission characteristics from a dye doped polymer optical fiber under two-photon excitation.

Two-photon excited (TPE) side illumination fluorescence studies in a Rh6G-RhB dye mixture doped polymer optical fiber (POF) and the effect of energy transfer on the attenuation coefficient is reported. The dye doped POF is pumped sideways using 800 nm, 70 fs laser pulses from a Ti:sapphire laser, and the TPE fluorescence emission is collected from the end of the fiber for different propagation distances. The fluorescence intensity of RhB doped POF is enhanced in the presence of Rh6G as a result of energy transfer from Rh6G to RhB. Because of the reabsorption and reemission process in dye molecules, an effective energy transfer is observed from the shorter wavelength part of the fluorescence spectrum to the longer wavelength part as the propagation distance is increased in dye doped POF. An energy transfer coefficient is found to be higher at shorter propagation distances compared to longer distances. A TPE fluorescence signal is used to characterize the optical attenuation coefficient in dye doped POF. The attenuation coefficient decreases at longer propagation distances due to the reabsorption and reemission process taking place within the dye doped fiber as the propagation distance is increased.

Hepatoprotection of Phyllanthus maderaspatensis against experimentally induced liver injury in rats.

The hexane extract of Phyllanthus maderaspatensis (200 and 100 mg/kg) showed significant hepatoprotection on carbon tetrachloride and thioacetamide induced liver damage in rats. The protective effect was evident from serum biochemical parameters and histopathological analysis. Rats treated with P. maderaspatensis remarkably prevented the elevation of serum AST, ALT and LDH and liver lipid peroxides in CCl(4) and thioacetamide treated rats. Hepatic glutathione levels significantly increased by the treatment with the extracts. Histopathological changes induced by CCl(4) and thioacetamide were also significantly reduced by the extract treatment. The activity of hexane extracts of P. maderaspatensis was comparable to that of silymarin, the reference hepatoprotective drug.

Effect of Cardiospermum halicacabum on ethanol-induced gastric ulcers in rats.

Ethanol extract of Cardiospermum halicacabum Linn. (Sapindaceae), in a concentration dependant manner (200-600mg/kg) inhibited gastric ulcers induced by oral administration of absolute ethanol. Further, the extract administration to rats resulted in an increase in levels of gastric glutathione and a decrease in alkaline phosphatase activity. The extract also exhibited potent in vitro hydroxyl radical scavenging and inhibition of lipid peroxidation activities. The extract was found to be devoid of any conspicuous acute and short-term toxicity in rats.