Cannabinoid therapeutics in orofacial pain management: a systematic review.

The objective of this paper was to investigate the published evidence regarding effects of cannabinoids (natural and synthetic) on post-operative and/or out-of-office pain management in patients suffering from orofacial pain that presents in the dental setting. Three online databases (Ovid (MEDLINE), PubMed (MEDLINE), Scopus) were searched (July 2021). Additional studies were sought through grey literature searching (Cochrane Library Trials and ClinicalTrials.gov) and hand-searching the reference lists of included articles. All studies that analysed cannabinoid products and pain management of conditions that present in the general or specialist dental setting in the English language were included. Of the five articles included, one reported a significant effect on temporomandibular disorder pain relief using a topical cannabidiol formulation compared to a placebo. Four articles reported no significant effects of cannabinoids for pain management across various orofacial pain conditions. Although one study reported a positive effect, insufficient evidence exists to support a tangible clinical benefit of cannabinoids in managing orofacial pain, further research is recommended to investigate the benefits of cannabinoids' use. © 2022 Australian Dental Association.

Long-term effects of feeding flaxseed on performance and egg fatty acid composition of brown and white hens.

Two hundred fifty-six 18-wk-old Shaver White and ISA-Brown pullets were fed commercial diets containing either 0 or 10% flaxseed in order to study the long-term effects of feeding flaxseed on hen performance and egg production parameters. Performance was monitored over 10 consecutive 28-d periods. Flaxseed was introduced gradually at 28 wk of age and was maintained until hens were 53 wk of age, when flaxseed was gradually eliminated from the diet. Feed intake was less (P < 0.05) for hens fed flaxseed compared to those consuming the control diet. Flax-fed hens were also lighter (P < 0.05) compared to the control birds. Egg production, egg weight, shell weight, albumen height, and shell thickness were not significantly (P > 0.05) different for hens consuming 0 and 10% flaxseed; however, yolk weight was reduced (P < 0.05) in hens fed flaxseed. Both strains of birds fed flaxseed deposited significantly more n-3 fatty acids into their eggs. Sampling of livers at the end of the trial showed that hens fed flaxseed had a higher (P < 0.05) incidence of liver hemorrhages.

Regulation of p53 expression by the RAS-MAP kinase pathway.

Activation of MAP kinase leads to the activation of p53-dependent pathways, and vice-versa. Although the amount of p53 protein increases in response to MAP kinase-dependent signaling, the basis of this increase is not yet fully understood. We have isolated the mutant cell line AP14, defective in p53 expression, from human HT1080 fibrosarcoma cells, which have an activated ras allele. The expression of p53 mRNA and protein is approximately 10-fold lower in AP14 cells than in the parental cells. The high constitutive phosphorylation and activities of the MAP kinases ERK1 and ERK2 in HT1080 cells are greatly reduced in AP14 cells, although the levels of these proteins are unchanged, suggesting that the defect in the mutant cells affects the steady-state phosphorylation of ERK1 and ERK2. Overexpression of ERK2 in AP14 cells restored both MAP kinase activity and p53 expression, and incubation of the mutant cells with the phosphatase inhibitor orthovanadate resulted in strong coordinate elevation of MAP kinase activity and p53 expression. The levels of expression of the p53-regulated gene p21 parallel those of p53 throughout, showing that basal p21 expression depends on p53. The levels of p53 mRNA increased by 5-8-fold when activated ras was introduced into wild-type cells, and the levels of the p53 and p21 proteins decreased substantially in wild-type cells treated with the MEK inhibitor U0216. We conclude that MAP kinase-dependent pathways help to regulate p53 levels by regulating the expression of p53 mRNA.

Regulation of ubiquitination and degradation of p53 in unstressed cells through C-terminal phosphorylation.

Previously, we found that the protein kinase C (PKC) inhibitor H7 stimulates p53 to accumulate in a form incapable of inducing transcription from p53-dependent promoters. We concluded that H7 inhibits constitutive C-terminal phosphorylation of p53, which regulates its turnover in unstressed cells. We now show that p53 and its inhibitor MDM2 (HDM2 in human cells) are together in the nuclei of H7-treated cells and can be co-immunoprecipitated. Despite this association of p53 with the ubiquitin ligase MDM2, ubiquitinated p53 was not detected in H7-treated cells. Furthermore, co-treatment with H7 and the proteosome inhibitor LLnL prevented the accumulation of ubiquitinated p53 that was observed in cells treated solely with LLnL. In addition, treatment of cells with the PKC activator phorbol ester stimulated the ubiquitination of p53 and reduced its ability to accumulate after stress. H7 did not induce the phosphorylation of human p53 on Ser-15 (Ser-18 in mouse protein), a modification that occurs in response to DNA damage and leads to the release of MDM2 and to transactivation by p53. We conclude that phosphorylation of the C-terminal domain of p53 by PKC increases its ubiquitination and degradation in unstressed cells.

Phosphorylation of serines 15 and 37 is necessary for efficient accumulation of p53 following irradiation with UV.

Changes in the phosphorylation state of p53 are important in increasing its half-life and potency as a transcription factor. To investigate their roles, serine residues 15 and 37 were mutated to alanines and the mutated proteins were expressed stably at low basal levels in Li-Fraumeni-derived p53-null human fibroblasts. The accumulation of p53 after DNA damage was analysed quantitatively in multiple clones. Mutation of serine 15, serine 37 or both impaired the accumulation of the protein after exposing the cells to ultraviolet radiation (50-100% increase for the mutant proteins, 500% increase for wild-type p53) but not after treatment with adriamycin. The diminished accumulation of mutant p53 protein is due to a reduction of basal HDM association. Analysis of p53-dependent transcription revealed that phosphorylation of serine 15 is required to maintain basal levels of p21 mRNA. These results provide new evidence for an important function of serine 37 phosphorylation, clearly distinguish the pathways of p53 activation in response to ultraviolet radiation or DNA damage inflicted by adriamycin, and reveal that serine 15 is crucial to support the p53-mediated basal expression of p21.

Analysis of the pdx-1 (snz-1/sno-1) region of the Neurospora crassa genome: correlation of pyridoxine-requiring phenotypes with mutations in two structural genes.

We report the analysis of a 36-kbp region of the Neurospora crassa genome, which contains homologs of two closely linked stationary phase genes, SNZ1 and SNO1, from Saccharomyces cerevisiae. Homologs of SNZ1 encode extremely highly conserved proteins that have been implicated in pyridoxine (vitamin B6) metabolism in the filamentous fungi Cercospora nicotianae and in Aspergillus nidulans. In N. crassa, SNZ and SNO homologs map to the region occupied by pdx-1 (pyridoxine requiring), a gene that has been known for several decades, but which was not sequenced previously. In this study, pyridoxine-requiring mutants of N. crassa were found to possess mutations that disrupt conserved regions in either the SNZ or SNO homolog. Previously, nearly all of these mutants were classified as pdx-1. However, one mutant with a disrupted SNO homolog was at one time designated pdx-2. It now appears appropriate to reserve the pdx-1 designation for the N. crassa SNZ homolog and pdx-2 for the SNO homolog. We further report annotation of the entire 36,030-bp region, which contains at least 12 protein coding genes, supporting a previous conclusion of high gene densities (12,000-13,000 total genes) for N. crassa. Among genes in this region other than SNZ and SNO homologs, there was no evidence of shared function. Four of the genes in this region appear to have been lost from the S. cerevisiae lineage.

The nop-1 gene of Neurospora crassa encodes a seven transmembrane helix retinal-binding protein homologous to archaeal rhodopsins.

Opsins are a class of retinal-binding, seven transmembrane helix proteins that function as light-responsive ion pumps or sensory receptors. Previously, genes encoding opsins had been identified in animals and the Archaea but not in fungi or other eukaryotic microorganisms. Here, we report the identification and mutational analysis of an opsin gene, nop-1, from the eukaryotic filamentous fungus Neurospora crassa. The nop-1 amino acid sequence predicts a protein that shares up to 81.8% amino acid identity with archaeal opsins in the 22 retinal binding pocket residues, including the conserved lysine residue that forms a Schiff base linkage with retinal. Evolutionary analysis revealed relatedness not only between NOP-1 and archaeal opsins but also between NOP-1 and several fungal opsin-related proteins that lack the Schiff base lysine residue. The results provide evidence for a eukaryotic opsin family homologous to the archaeal opsins, providing a plausible link between archaeal and visual opsins. Extensive analysis of Deltanop-1 strains did not reveal obvious defects in light-regulated processes under normal laboratory conditions. However, results from Northern analysis support light and conidiation-based regulation of nop-1 gene expression, and NOP-1 protein heterologously expressed in Pichia pastoris is labeled by using all-trans [3H]retinal, suggesting that NOP-1 functions as a rhodopsin in N. crassa photobiology.

Straightforward solid-phase extraction method for the determination of verapamil and its metabolite in plasma in a 96-well extraction plate.

Straightforward solid-phase extraction (SPE) methods were developed for the determination of verapamil and its metabolite in a plasma matrix. The spiked plasma sample was pretreated with 2% phosphoric acid followed by two different SPE methods using a Waters Oasis HLB 96-well extraction plate. Recoveries greater than 90% were obtained using both a generic and a selective SPE methods. The generic method is a good starting protocol, and it is applicable to a wide range of compounds. This generic method consists of using 5% methanol as the wash solvent, and 100% methanol for the elution. The limitation of the non-specific method is that it does not remove all plasma constituents that interfere with the quantitation of the metabolite, norverapamil. A second, more specific method was developed using the same Oasis HLB sorbent which removes more plasma interferences and provides cleaner extracts for the HPLC-UV analysis. This selective method uses both the methanol concentration and the pH advantageously to preferentially isolate the analytes of interest from a complex sample matrix. Recoveries of greater than 90% with R.S.D.s less than 3.8% were obtained with this selective method.

Expressed sequences from conidial, mycelial, and sexual stages of Neurospora crassa.

In the Neurospora Genome Project at the University of New Mexico, expressed sequence tags (ESTs) corresponding to three stages of the life cycle of the filamentous fungus Neurospora crassa are being analyzed. The results of a pilot project to identify expressed genes and determine their patterns of expression are presented. 1,865 partial complementary DNA (cDNA) sequences for 1,409 clones were determined using single-pass sequencing. Contig analysis allowed the identification of 838 unique ESTs and 156 ESTs present in multiple cDNA clones. For about 34% of the sequences, highly or moderately significant matches to sequences (of known and unknown function) in the NCBI database were detected. Approximately 56% of the ESTs showed no similarity to previously identified genes. Among genes with assigned function, about 43.3% were involved in metabolism, 32.9% in protein synthesis and 8.4% in RNA synthesis. Fewer were involved in defense (6%), cell signalling (3.4%), cell structure (3.4%) and cell division (2.6%).

Pericoronal radiolucencies with and without radiopacities.

Pericoronal radiolucencies are common entities of the jaws that account for about 15% to 20% of all biopsy specimens. They are usually slow-growing, benign entities that involve odontogenic epithelium and the crown of a nonerupting tooth. Many lesions develop early in life and are detected during routine radiographic examination. Others are found in later years when a patient presents with a slow-growing swelling. The dentist is often the first provider to encounter these conditions. Thus, he or she must be familiar with their appearance and understand the proper management required.

Cardiac imaging after acute myocardial infarction. Identification of patients at continued risk.

Diagnostic imaging performed early in the course of acute myocardial infarction provides anatomic and functional information that is useful in assessing patients at risk for future cardiac events and premature death. Early identification of left ventricular dysfunction or complications of myocardial infarction allows appropriate and timely management of high-risk patients and early transfer of stable patients from the intensive care environment. Noninvasive predischarge functional imaging to unmask patients with jeopardized myocardium identifies high-risk patients who may need invasive studies and surgical or interventional treatment. Postdischarge risk stratification with diagnostic imaging provides vital prognostic information in high- and low-risk patients, allowing for appropriate allocation of medical resources.

Phosphorylation of chicken cardiac C-protein by calcium/calmodulin-dependent protein kinase II.

Chicken cardiac C-protein was readily phosphorylated by purified calcium/calmodulin-dependent protein kinase II (CaM-kinase II). Maximum incorporation was about 4 mol of 32P/mol of C-protein subunit. Peptide mapping indicated that some of the sites phosphorylated by CaM-kinase II were located on the same phosphopeptides obtained when C-protein was phosphorylated by the cAMP-dependent protein kinase (peptides T1, T2, and T3). There was a fourth peptide (T3a) which was unique to CaM-kinase II phosphorylation. 32P-Amino acid analysis showed that essentially all of the 32P of peptides T1, T2, and T3a was in phosphoserine. cAMP-dependent protein kinase incorporated 32P only into threonine of peptide T3. Threonine was the preferred site of phosphorylation by CaM-kinase II, but there was significant phosphorylation of a serine in peptide T3. Partially purified C-protein preparations contained an associated calcium/calmodulin-dependent protein kinase. Peptide maps obtained from C-protein phosphorylated by the endogenous kinase were similar to those obtained from C-protein phosphorylated by CaM-kinase II. However, the ratio of phosphothreonine to phosphoserine in peptide T3 was lower. This was due to a contaminating phosphatase in the partially purified C-protein which preferentially dephosphorylated the phosphothreonine of peptide T3. It is suggested that the calcium/calmodulin-dependent protein kinase associated with C-protein is similar or identical to CaM-kinase II and that CaM-kinase II may play a role in the phosphorylation of C-protein in the heart.

Radiolucent halos associated with radiopaque composite resin restorations.

Since the introduction of radiopaque composite resins, clinicians and researchers have occasionally noticed radiolucent halos adjacent to composite restorations. Such halos have frequently been thought to be recurrent caries or voids in the material. Fifteen of 45 radiopaque composite resin restorations placed by students enrolled in a first-year preclinical operative dentistry course exhibited such halos. Micrographs showed that a thick layer of unfilled resin bonding agent was present. These halos were reproduced in other teeth when excess bonding was not blown off. The results indicate the importance of meticulous technique.

Differential paternity in Libya.

PIP: Libyan census and vital statistics data from 1973 are compared with genealogical records from Utah males born between 1830 and 1834 as representative of populations not using any method of fertility control. The Libyan vital statistics data contained 97% of paternity by age, but only 85% of maternity by age. These missing data were distributed pro rata, and all data were corrected for errors in reporting. Polygamous unions were excluded because polygamy is relatively rare in Libya. The Utah data were from 185,000 genealogies of the Genealogical Society of Utah. The Libyan child-woman ratio (number of children under age 5 per number of women aged 15-49) is 1112.9, compared to 850 in Morocco, suggesting that Libya is experiencing an increase in fertility, in child survival and probably in quality of statistics. The total fertility rates for females were 11.1 for Libya and 11.2 for Utah; the total paternity rates were 14.3 and 13.7, respectively. Male rates are higher because of remarriage after divorce or death of wives. Age-specific paternity rates are tabulated and graphed: The major difference between the 2 populations is the concave shape of the curve for Libyan men under 30. Age at marriage is late, but marriage is virtually universal for Libyan men over 30. Age-specific paternity rates by occupation show apparent lack of fertility regulation in traditional occupations like farming and sales. There is evidence of some parity-related fertility control in professional and administrative workers. Production workers have a high peak in fertility around age 27.5 and 32.5, and a dip occurring at older ages. These figures can be explained by education, since education is required for professional occupations, and older professionals were trained in the West. Production workers took advantage of rapidly expanding education in Libya late in their youth, postponing marriage. Libya's pronatalist policy forbids sale of contraceptives and provides child allowances, free education, health care, subsidized housing and social security. This paper indicates the utility of paternity data where statistics on maternity are unavailable.^ieng

Significance of condylar positions in patients with temporomandibular disorders.

Radiographs of closed condylar positions in subjects with symptoms of temporomandibular joint disorders are compared with those in subjects without symptoms. Of the condyles in asymptomatic subjects, 30% had anterior or posterior deviations of more than 1 mm in either direction. Of the condyles in symptomatic subjects, 27% had anterior or posterior deviations of more than 1 mm. As the findings are almost the same for both groups, it appears that condylar position in the fossa, as determined by transcranial radiographs, is of questionable significance as it relates to the symptoms of temporomandibular disorders.

Birth spacing and fertility limitation: a behavioral analysis of a nineteenth century frontier population.

Our analysis of changing birth interval distributions over the course of a fertility transition from natural to controlled fertility has examined three closely related propositions. First, within both natural fertility populations (identified at the aggregate level) and cohorts following the onset of fertility limitation, we hypothesized that substantial groups of women with long birth intervals across the individually specified childbearing careers could be identified. That is, even during periods when fertility behavior at the aggregate level is consistent with a natural fertility regime, birth intervals at all parities are inversely related to completed family size. Our tabular analysis enables us to conclude that birth spacing patterns are parity dependent; there is stability in CEB-parity specific mean and birth interval variance over the entire transition. Our evidence does not suggest that the early group of women limiting and spacing births was marked by infecundity. Secondly, the transition appears to be associated with an increasingly larger proportion of women shifting to the same spacing schedules associated with smaller families in earlier cohorts. Thirdly, variations in birth spacing by age of marriage indicate that changes in birth intervals over time are at least indirectly associated with age of marriage, indicating an additional compositional effect. The evidence we have presented on spacing behavior does not negate the argument that parity-dependent stopping behavior was a powerful factor in the fertility transition. Our data also provide evidence of attempts to truncate childbearing. Specifically, the smaller the completed family size, the longer the ultimate birth interval; and ultimate birth intervals increase across cohorts controlling CEB and parity. But spacing appears to represent an additional strategy of fertility limitation. Thus, it may be necessary to distinguish spacing and stopping behavior if one wishes to clarify behavioral patterns within a population (Edlefsen, 1981; Friedlander et al., 1980; Rodriguez and Hobcraft, 1980). Because fertility transition theories imply increased attempts to limit family sizes, it is important to examine differential behavior within subgroups achieving different family sizes. It is this level of analysis which we have attempted to achieve in utilizing parity-specific birth intervals controlled by children ever born.(ABSTRACT TRUNCATED AT 400 WORDS)