Terpenes and Cannabinoids Yields and Profile from Direct-Seeded and Transplanted CBD-Cannabis sativa.

Following recent legalization, the production of hemp (Cannabis sativa L.) for high-value plant compounds became a major crop in many countries across the world. In this study, we profiled popular plant compounds being extracted for emerging markets, terpenes and cannabinoids, developed in two different planting systems of a single, high-cannabidiol (CBD), low-Δ9-tetrahydrocannabinol (Δ9-THC), dioecious hemp cultivar 'Culver' in central Oregon, U.S.A. One system is the current conventional system of an open, all-female, clonal transplant (OFCT) production system. This is compared to a dioecious, densely seeded (DDS) production system. Overall, the essential oil (EO, chiefly terpenes) and cannabinoid profiles of plants harvested from the two systems were comparable. In comparison to the DDS plots, the EO obtained from colas of the OFCT plots had higher concentrations of α-pinene, myrcene, limonene, ß-bisabolene, γ-cadinene, caryophyllene oxide, guaiol, 10-epi-γ-eudesmol, ß-eudesmol, bulnesol, epi-α-bisabolol, α-humulene, and CBD, although lower concentrations of 1,8-cineole, (E)-caryophyllene, γ-elemene, α-selinene, selina-4(15),7(11)-diene, selina-3,7(11)-diene, and germacrene B. Of the various plant parts (female leaves and chaff, male flowers) tested in the DDS plots, the highest EO yield was obtained from the chaff. The main EO constituents of female leaves were (E)-caryophyllene (14-21%), caryophyllene oxide (13-16%), α-humulene (5-6%), humulene epoxide II (3.5-3.8%), epi-α-bisabolol (2.7-5.5%), CBD, and α-eudesmol (1.1-2.6%). The principal EO constituents of female chaff from the DDS system were (E)-caryophyllene (∼21%), α-humulene (6.6%), ß-selinene (4.5%), α-selinene (3.6%), selina-3,7(11)-diene (9.8%), selina-4(15),7(11)-diene (6.3%), caryophyllene oxide (5.2%), and cannabichromene (3.1%). The major EO constituents of the male flowers were CBD (19.3%), caryophyllene oxide (11%), α-humulene (4.1%), epi-α-bisabolol (3.9%), selina-3,7(11)-diene (3.4%), and ß-selinene (3.4%). Cannabinoids were not detected in the EO distilled for 30 min, but they were present in the EO from 240 min of distillation. The EO content of female leaves and male flowers was relatively low, whereas the EO content of the female chaff from the DDS system was significantly greater. Breaking with conventional knowledge, the EO of male flowers may accumulate up to 19% CBD. Distillation of plants from both production systems converted CBD-A to CBD, CBDV-A to CBDV, CBG-A to CBG, and THC-A to THC as a result of the thermal decarboxylation of acidic cannabinoids but otherwise did not affect the total cannabinoid content. Most of the cannabinoids remained in the distilled biomass after the extraction of terpenes (EO). Therefore, the distilled, terpene-free biomass represents a high-value product that could be further extracted for cannabinoids or used as a component in various products.

Home Exercises Versus On-Site Rehabilitation in the Management of Lateral Elbow Tendinopathy: A Critically Appraised Topic.

Clinical Scenario: Lateral elbow tendinopathy (LE) is a common musculoskeletal condition that often results in pain and disability. An array of conservative interventions have been shown to improve patient outcomes in outpatient rehabilitation clinics. However, with the rise in health care costs, patients and rehabilitation specialists have opted to reduce the number of in-house visits and focus on home exercise programs (HEPs). As a result, many rehabilitation specialists and patients now depend on HEPs as the primary intervention to treat LE. Focused Clinical Question: For individuals with LE, is there evidence to suggest that HEPs are as effective as traditional on-site rehabilitation for reducing pain and disability? Summary of Search, Best Evidence Appraised, and Key Findings: The literature was searched for studies comparing HEP to on-site rehabilitation in the management of LE. Two clinical controlled trials (CCTs) were included. No studies suggested that HEPs demonstrated equal or improved outcomes in pain or disability. Both studies concluded that on-site rehabilitation services were more effective at reducing pain and disability in the short term. More research is needed to compare the cost effectiveness of both HEP and on-site rehabilitation. Clinical Bottom Line: Based on 2 CCTs, it can be concluded that there is moderate evidence to suggest that patients with LE experience decreased pain and disability scores with on-site rehabilitation compared to a guided HEP in the short term. The authors could not draw a conclusion regarding long-term effects of treatments or cost effectiveness of the 2 approaches. Strength of Recommendation: Based on the Centre for Evidence Based Medicine, there is level B evidence that a HEP only was not as effective as on-site rehabilitation services in patients with LE.

A Pathological Analysis of Canaliculitis Concretions: More Than Just Actinomyces.

Purpose. Canaliculitis is classically associated with Actinomyces species, which are filamentous bacteria; the purpose of this study was to evaluate the extent to which nonfilamentous bacteria colonize canalicular concretions by using graded histopathological analysis. Methods. This is a series of 16 cases. The percentage of Gram-positive/Gomori's methenamine silver-positive filamentous bacteria (Actinomyces) versus the total bacteria identified was graded, and the types of bacteria seen were recorded. Nonfilamentous bacteria were categorized based upon Gram stain (positive or negative) and morphology (cocci or rods). Results. There were 11 females and 5 males. Nonfilamentous bacteria were identified in 16 of 16 (100%) specimens and filamentous bacteria were identified in 15 of 16 (94%) specimens. The mean percentage of filamentous bacteria relative to total bacteria was 57%. Regarding the nonfilamentous bacteria present, 69% of specimens had Gram-positive cocci only, 25% had Gram-positive and Gram-negative cocci, and 6% had Gram-positive cocci and Gram-positive rods. Conclusion. In the current study, there was a mix of filamentous and nonfilamentous bacteria in almost all canalicular concretions analyzed. Nonfilamentous bacteria may contribute to the pathogenesis of canaliculitis. In addition, the success of bacterial culture can be variable; therefore, pathological analysis can assist in determining the etiology.

Isolated epididymal injury after blunt scrotal trauma from high velocity paintball round.

Isolated epididymal injury without associated underlying scrotal or testicular injury in the setting of blunt trauma is exceedingly rare. We present a case of an isolated epididymal injury incurred after scrotal trauma from a high velocity paintball round. Ultrasound demonstrated an enlarged, hypoechoic left epididymis with no evidence of underlying testicular injury. This case highlights the importance of obtaining imaging to evaluate for signs of testicular rupture, potentially obviating the need for surgery. It also reinforces the need for appropriate protective gear when participating in activities with potential for high velocity scrotal trauma.

Malakoplakia of the prostate masquerading as locally advanced prostate cancer on mpMRI.

A 66-year-old man was referred for urological evaluation for an abnormal digital rectal exam (cT2a, subtle nodule at left base, 121 cc prostate) and an elevated prostate specific antigen (PSA) of 8.0 ng/ml. Subsequent 12-core transrectal ultrasound (TRUS)-guided biopsy revealed Gleason 3+4 adenocarcinoma in seven of 12 cores, including all six cores on the right side and one core at the left apex. No extraprostatic extension was identified. Post-biopsy, the patient developed urinary retention requiring a catheter, as well as an Escherichia coli (E. coli) urinary tract infection (UTI) requiring hospitalization and intravenous antibiotics.

Late renal vein aneurysm following living related renal transplant.

Renal vein aneurysms are rare; there are less than 10 reported cases. As of yet there have been no reported cases of renal vein aneurysm following renal transplantation. We present a case of an incidentally discovered renal vein aneurysm following uncomplicated living related renal transplant. The lesion was discovered 4 years after the transplant through abdominal ultrasound investigation of new right lower quadrant discomfort. Magnetic resonance imaging confirmed the presence of a 2.3-cm thrombosed renal vein aneurysm of the main renal vein. This case report highlights the rare nature of these events, the diagnostic challenges and the lack of satisfactory management guidelines in these cases.

A fluorescent biosensor reveals conformational changes in human immunoglobulin E Fc: implications for mechanisms of receptor binding, inhibition, and allergen recognition.

IgE binding to its high affinity receptor FcεRI on mast cells and basophils is a key step in the mechanism of allergic disease and a target for therapeutic intervention. Early indications that IgE adopts a bent structure in solution have been confirmed by recent x-ray crystallographic studies of IgEFc, which further showed that the bend, contrary to expectation, is enhanced in the crystal structure of the complex with receptor. To investigate the structure of IgEFc and its conformational changes that accompany receptor binding in solution, we created a Förster resonance energy transfer (FRET) biosensor using biologically encoded fluorescent proteins fused to the N- and C-terminal IgEFc domains (Cε2 and Cε4, respectively) together with the theoretical basis for quantitating its behavior. This revealed not only that the IgEFc exists in a bent conformation in solution but also that the bend is indeed enhanced upon FcεRI binding. No change in the degree of bending was seen upon binding to the B cell receptor for IgE, CD23 (FcεRII), but in contrast, binding of the anti-IgE therapeutic antibody omalizumab decreases the extent of the bend, implying a conformational change that opposes FcεRI engagement. HomoFRET measurements further revealed that the (Cε2)(2) and (Cε4)(2) domain pairs behave as rigid units flanking the conformational change in the Cε3 domains. Finally, modeling of the accessible conformations of the two Fab arms in FcεRI-bound IgE revealed a mutual exclusion not seen in IgG and Fab orientations relative to the membrane that may predispose receptor-bound IgE to cross-linking by allergens.

Birth statistics for African (Loxodonta africana) and Asian (Elephas maximus) elephants in human care: history and implications for elephant welfare.

African (Loxodonta africana) and Asian elephants (Elephas maximus) have lived in the care of humans for many years, yet there is no consensus concerning some basic parameters describing their newborn calves. This study provides a broad empirical basis for generalizations about the birth heights, birth weights, birth times and gestation periods of elephant calves born in captivity. I obtained data concerning at least one of these four characteristics for 218 newborn calves from 74 institutions. Over the past 30 years, newborn Asian elephants have been taller and heavier than newborn African elephants. Neonatal African elephants exhibited sex differences in both weight and height, whereas neonatal Asian elephants have exhibited sex differences only in height. Primiparous dams ex situ are at least as old as their in situ counterparts, whereas ex situ sires appear to be younger than sires in range countries. Confirming earlier anecdotal evidence, both African [N=47] and Asian [N=91] dams gave birth most often at night.

A survey of the management and development of captive African elephant (Loxodonta africana) calves: birth to three months of age.

We used four surveys to collect information about the birth, physical growth, and behavioral development of 12 African elephant calves born in captivity. The management of the birth process and neonatal care involved a variety of standard procedures. All of the calves were born at night, between 7PM and 7AM. The calves showed a systematic progression in behavioral and physical development, attaining developmental milestones at least a quickly as calves in situ. This study emphasized birth-related events, changes in the ways that calves used their trunks, first instances of behaviors, and interactions of the calves with other, usually adult, elephants. Several behaviors, such as the dam covering her calf with hay and the calf sucking its own trunk, were common in the captive situation and have been observed in situ. Overall, the behaviors of the calves resembled those observed for African elephant calves in situ. These data should help in the management of African elephants under human care by providing systematic reference values for the birth and development of elephant calves.

Initial findings on visual acuity thresholds in an African elephant (Loxodonta africana).

There are only a few published examinations of elephant visual acuity. All involved Asian elephants (Elephas maximus) and found visual acuity to be between 8' and 11' of arc for a stimulus near the tip of the trunk, equivalent to a 0.50 cm gap, at a distance of about 2 m from the eyes. We predicted that African elephants (Loxodonta africana) would have similarly high visual acuity, necessary to facilitate eye-trunk coordination for feeding, drinking and social interactions. When tested on a discrimination task using Landolt-C stimuli, one African elephant cow demonstrated a visual acuity of 48' of arc. This represents the ability to discriminate a gap as small as 2.75 cm in a stimulus 196 cm from the eye. This single-subject study provides a preliminary estimate of the visual acuity of African elephants.

Conformation and dynamics of a rhodamine probe attached at two sites on a protein: implications for molecular structure determination in situ.

Replica exchange molecular dynamics (REMD) calculations were used to determine the conformation and dynamics of bifunctional rhodamine probes attached to pairs of cysteines in three model systems: (a) a polyalanine helix, (b) the isolated C helix (residues 53-66) of troponin C, and (c) the C helix of the N-terminal region (residues 1-90) of troponin C (sNTnC). In each case, and for both diastereoisomers of each probe-protein complex, the hydrophobic face of the probe is close to the protein surface, and its carboxylate group is highly solvated. The visible-range fluorescence dipole of the probe is approximately parallel to the line joining the two cysteine residues, as assumed in previous in situ fluorescence polarization studies. The independent rotational motion of the probe with respect to the protein on the nanosecond time scale is highly restricted, in agreement with data from fluorescence polarization and NMR relaxation studies. The detailed interaction of the probe with the protein surface depends on steric factors, electrostatic and hydrophobic interactions, hydrogen bonds, and hydration effects. The interaction is markedly different between diastereoisomers, and multiple preferred conformations exist for a single diasteroisomer. These results show that the combination of the hydrophobic xanthylium moiety of bifunctional rhodamine with the carboxylate substitution in its pendant phenyl ring causes the probe to be immobilized on the protein surface, while the two-site cysteine attachment defines the orientation of its fluorescence dipole. These features allow the orientation of protein components to be accurately determined in situ by polarized fluorescence measurements from bifunctional rhodamine probes.

Toward protein structure in situ: comparison of two bifunctional rhodamine adducts of troponin C.

As part of a program to develop methods for determining protein structure in situ, sTnC was labeled with a bifunctional rhodamine (BR or BSR), cross-linking residues 56 and 63 of its C-helix. NMR spectroscopy of the N-terminal domain of BSR-labeled sTnC in complex with Ca(2+) and the troponin I switch peptide (residues 115-131) showed that BSR labeling does not significantly affect the secondary structure of the protein or its dynamics in solution. BR-labeling was previously shown to have no effect on the solution structure of this complex. Isometric force generation in isolated demembranated fibers from rabbit psoas muscle into which BR- or BSR-labeled sTnC had been exchanged showed reduced Ca(2+)-sensitivity, and this effect was larger with the BSR label. The orientation of rhodamine dipoles with respect to the fiber axis was determined by polarized fluorescence. The mean orientations of the BR and BSR dipoles were almost identical in relaxed muscle, suggesting that both probes accurately report the orientation of the C-helix to which they are attached. The BSR dipole had smaller orientational dispersion, consistent with less flexible linkers between the rhodamine dipole and cysteine-reactive groups.

The locomotor kinematics of Asian and African elephants: changes with speed and size.

For centuries, elephant locomotion has been a contentious and confusing challenge for locomotion scientists to understand, not only because of technical difficulties but also because elephant locomotion is in some ways atypical of more familiar quadrupedal gaits. We analyzed the locomotor kinematics of over 2400 strides from 14 African and 48 Asian elephant individuals (body mass 116-4632 kg) freely moving over ground at a 17-fold range of speeds, from slow walking at 0.40 m s(-1) to the fastest reliably recorded speed for elephants, 6.8 m s(-1). These data reveal that African and Asian elephants have some subtle differences in how size-independent kinematic parameters change with speed. Although elephants use a lateral sequence footfall pattern, like many other quadrupeds, they maintain this footfall pattern at all speeds, shifting toward a 25% phase offset between limbs (singlefoot) as they increase speed. The duty factors of elephants are greater for the forelimbs than for the hindlimbs, so an aerial phase for the hindquarters is reached at slower speeds than for the forequarters. This aerial phase occurs at a Froude number of around 1, matching theoretical predictions. At faster speeds, stance and swing phase durations approach asymptotes, with the duty factor beginning to level off, concurrent with an increase in limb compliance that likely keeps peak forces relatively low. This increase of limb compliance is reflected by increased compression of the hindlimbs. Like other tetrapods, smaller elephants are relatively more athletic than larger ones, but still move very similarly to adults even at <500 kg. At any particular speed they adopt greater relative stride frequencies and relative stride lengths compared to larger elephants. This extends to near-maximal locomotor performance as well - smaller elephants reach greater Froude numbers and smaller duty factors, hence likely reach relatively greater peak loads on their limbs and produce this force more rapidly. A variety of lines of kinematic evidence support the inference that elephants change their mechanics near a Froude number of 1 (if not at slower speeds), at least to using more compliant limbs, if not spring-like whole-body kinetics. In some ways, elephants move similarly to many other quadrupeds, such as increasing speed mainly by increasing stride frequency (except at fast speeds), and they match scaling predictions for many stride parameters. The main difference from most other animals is that elephants never change their footfall pattern to a gait that uses a whole-body aerial phase. Our large dataset establishes what the normal kinematics of elephant locomotion are, and can also be applied to identify gait abnormalities that may signal musculoskeletal pathologies, a matter of great importance to keepers of captive elephants.

Identifiability analysis of models for reversible intermolecular two-state excited-state processes coupled with species-dependent rotational diffusion monitored by time-resolved fluorescence depolarization.

A deterministic identifiability analysis of the kinetic model for a reversible intermolecular two-state excited-state process with species-dependent rotational diffusion described by Brownian reorientation is presented. The cases of both spherically and cylindrically symmetric rotors, with no change in the principal axes of rotation on interconversion in the latter case, are specifically considered. The identifiability analysis is carried out in terms of compartmental modeling based on the S(t) identical with I( parallel)(t)+2I( perpendicular)(t) and D(t) identical with I( parallel)(t)-I( perpendicular)(t) functions, where I( parallel)(t) and I( perpendicular)(t) are the delta-response functions for fluorescence, polarized, respectively, parallel and perpendicular to the electric vector of linearly polarized excitation. It is shown that, from polarized time-resolved fluorescence data collected at two concentrations of coreactant and three appropriately chosen emission wavelengths, (a) a unique set of rate constants for the overall excited-state process is always obtained by making use of polarized measurements and (b) the rotational diffusion constants and geometrical factors associated with the different anisotropy decay components can be uniquely determined and assigned to each species. The geometrical factors are determined by the absorption and emission transitions in the two rotating species. For spherical rotors, these factors depend directly on the relative orientations of the transition moments, while for cylindrically symmetric rotors they depend on the orientations with respect to each other and to the symmetry axis.

Bilateral organization of unilaterally generated activity in lumbar spinal motoneurons of the rat.

The spinal nucleus of the bulbocavernosus (SNB) is a medially located, bilaterally organized sexually dimorphic motor nucleus in the lumbar spinal cord of the male rat. To begin to assess the potential functional significance of this bilateral organization, we recorded ipsi- and contralateral SNB motor nerve activity following unilateral spinal stimulation and examined the timing, pattern, and recruitment of population motoneuron activity. A possible mechanism for bilateral communication, gap junctional intercellular communication, was also investigated because dye coupling experiments indicate an extensive syncytium in which SNB motoneurons are coupled with each other and neighboring interneurons. An in vivo peripheral nerve recording paradigm was used: a bipolar stimulating electrode was placed on dorsal root L6, and bipolar recording electrodes were placed bilaterally on the SNB motor nerves. All processes were severed distal to electrode placement to isolate the central preparation; recruitment curves of motoneuronal activity were then generated. Amplitude of peak to peak recruitment was greater in the contralateral motor nerve than in the ipsilateral nerve. Response latency, Fourier transform and spike counts showed no evidence of ipsi/contralateral asymmetry. Recruitment was attenuated both ipsi- and contralaterally after pharmacological gap junction blockade, but antidromic stimulation could not drive activity in contralateral motor axons. These results indicate that unilateral input to the SNB may be differentially modulated to produce functionally distinct output in the two separate halves of the nucleus. We also discuss the potential modulatory role of gap junctions in the activity of the SNB.

Oral complications in cancer chemotherapy, cancer incidence, and mortality in the U.S.

Cancer is the second-leading cause of death in the United States. Patients treated with chemotherapy, especially patients undergoing bone marrow and peripheral stem cell transplants, frequently suffer oral complications. The dentist is responsible for detecting and treating all active and potential sources of oral infection, in addition to providing follow-up care for the patient, in a manner that does not delay the treatment of the cancer.

Bifunctional rhodamine probes of Myosin regulatory light chain orientation in relaxed skeletal muscle fibers.

The orientation of the regulatory light chain (RLC) region of the myosin heads in relaxed skinned fibers from rabbit psoas muscle was investigated by polarized fluorescence from bifunctional rhodamine (BR) probes cross-linking pairs of cysteine residues introduced into the RLC. Pure 1:1 BR-RLC complexes were exchanged into single muscle fibers in EDTA rigor solution for 30 min at 30 degrees C; approximately 60% of the native RLC was removed and stoichiometrically replaced by BR-RLC, and >85% of the BR-RLC was located in the sarcomeric A-bands. The second- and fourth-rank order parameters of the orientation distributions of BR dipoles linking RLC cysteine pairs 100-108, 100-113, 108-113, and 104-115 were calculated from polarized fluorescence intensities, and used to determine the smoothest RLC orientation distribution-the maximum entropy distribution-consistent with the polarized fluorescence data. Maximum entropy distributions in relaxed muscle were relatively broad. At the peak of the distribution, the "lever" axis, linking Cys707 and Lys843 of the myosin heavy chain, was at 70-80 degrees to the fiber axis, and the "hook" helix (Pro830-Lys843) was almost coplanar with the fiber and lever axes. The temperature and ionic strength of the relaxing solution had small but reproducible effects on the orientation of the RLC region.

Testosterone manipulation protects motoneurons from dendritic atrophy after contralateral motoneuron depletion.

Dendritic morphology is reactive to many kinds of injuries, including axotomy and deafferentation. In this study, we examined the response of motoneurons in the spinal nucleus of the bulbocavernosus (SNB), an androgen-dependent population of motoneurons in the lumbar spinal cord of the rat, to partial motoneuron depletion. We depleted SNB motoneurons on one side only of the spinal cord by unilateral intramuscular injection of a retrogradely transported form of saporin, and examined the morphology of contralateral SNB motoneurons. Motoneuron morphology was assessed in normal control males, gonadally intact saporin-treated males, and saporin-treated males who had been castrated 6 weeks previously and given testosterone replacement beginning at the time of saporin injection. Untreated castrated males served as an additional control group. Four weeks after saporin treatment, SNB motoneurons contralateral to the saporin injection were retrogradely labeled with horseradish peroxidase conjugated to the cholera toxin B subunit and reconstructed in three dimensions. In gonadally intact males, unilateral motoneuron depletion caused regressive changes in contralateral SNB motoneurons: Soma size and dendritic length were both decreased. However, testosterone manipulation (i.e., castration followed by testosterone replacement) completely prevented the dendritic retraction. These data suggest a therapeutic role for testosterone in preventing, or accelerating recovery from, dendritic atrophy induced by motoneuron injury.

Oral complications in radiation therapy.

The dentist is integral to managing care for patients with head and neck cancer. Oral complications may manifest during and/or following radiation therapy and can last for the lifetime of the individual. This article reviews a number of these complications as well as the resources available to dentists for managing care of radiation oncology patients and improving their quality of life.