Sleep is required to consolidate odor memory and remodel olfactory synapses.

Animals with complex nervous systems demand sleep for memory consolidation and synaptic remodeling. Here, we show that, although the Caenorhabditis elegans nervous system has a limited number of neurons, sleep is necessary for both processes. In addition, it is unclear if, in any system, sleep collaborates with experience to alter synapses between specific neurons and whether this ultimately affects behavior. C. elegans neurons have defined connections and well-described contributions to behavior. We show that spaced odor-training and post-training sleep induce long-term memory. Memory consolidation, but not acquisition, requires a pair of interneurons, the AIYs, which play a role in odor-seeking behavior. In worms that consolidate memory, both sleep and odor conditioning are required to diminish inhibitory synaptic connections between the AWC chemosensory neurons and the AIYs. Thus, we demonstrate in a living organism that sleep is required for events immediately after training that drive memory consolidation and alter synaptic structures.

Tumor suppressor gene mutation in a patient with a history of hyperparathyroidism-jaw tumor syndrome and healed generalized osteitis fibrosa cystica: a case report and genetic pathophysiology review.

Hyperparathyroidism-jaw tumor (HPT-JT) was first observed by Jackson in 1958 in a family who exhibited hyperparathyroidism and recurrent pancreatitis. The author noticed the presence of jaw tumors in the affected family and reported them as fibrous dysplasia. However, it was not until 1990 that a familial variety of hyperparathyroidism with fibro-osseous jaw tumors was recognized as HPT-JT syndrome and reported as a clinically and genetically distinct syndrome. Hyperparathyroidism generally arises from glandular hyperplasia or parathyroid adenomas, with only about 1% of cases resulting from parathyroid carcinoma. However, parathyroid carcinoma develops in about 15% of HPT-JT patients. The true incidence of HPT-JT is unknown, although the prevalence of about 100 published cases suggests its rarity. Twenty percent of HPT-JT cases have renal hamartomas or tumors, and female patients with HPT-JT have been reported to have carcinoma of the uterus. This syndrome appears to arise from a variety of mutations that deactivate the tumor suppressor gene CDC73 (also known as HRPT2) and its production of the tumor suppressor protein parafibromin. Functional parafibromin has 531 amino acids, and mutations result in a short nonfunctional protein. CDC73 disorders exhibit dominant germline gene behavior, with varying degrees of penetration. In most cases an affected person has 1 parent with the condition, which raises the need for family investigation and genetic counseling. We report a case of HPT-JT syndrome in a male patient who presented to the local community hospital 6 years previously with a history of back pain. Investigations showed elevated serum parathyroid hormone and calcium levels, and a technetium 99m sestamibi parathyroid scan showed increased activity at the site of the lower left gland that proved to be a substernal parathyroid carcinoma. The patient's parathyroid hormone level dropped from 126 to 97 pg/mL at 5 minutes and was 65 pg/mL at 10 minutes after excision of the gland, and the calcium chemistry findings returned to normal. Parathyroid histologic analysis showed substantial cytologic atypia with nuclear pleomorphism and prominent nucleoli, but infrequent mitoses. Although the capsule was described as showing foci of vascular invasion by the carcinoma, there has been no evidence of recurrence. Six years later, the patient presented with bilateral mandibular cemento-ossifying fibromas, but no evidence of hyperparathyroidism. The larger left tumor was excised and immediately reconstructed with an autogenous iliac crest bone graft, and the right lesion was enucleated. There has been no recurrence in 12 months. This case illustrates that the hyperparathyroidism and the fibro-osseous tumors are independent features of the persistent germline tumor suppressor gene (CDC73) mutation. The syndromic fibro-osseous tumors are odontogenic cemento-ossifying fibromas, which only occur in the jaws.

Oral and maxillofacial surgery and chronic painful temporomandibular disorders--a systematic review.

PURPOSE: To provide a systematic review of the best available research literature investigating the relation of oral and maxillofacial surgical procedures to the onset or relief of chronic painful temporomandibular disorder (TMD). MATERIALS AND METHODS: A comprehensive review of the databases CINAHL, Cochrane Library, Embase, Medline, NHS Evidence--Oral Health, PsycINFO, Web of Knowledge, and MetaLib was undertaken by 2 authors (P.S., M.H.) up to June 2009 using search terms appropriate to establishing a relation between orofacial surgical procedures and TMD. The search was restricted to English-language publications. RESULTS: Of the 1,777 titles reviewed, 35 articles were critically appraised but only 32 articles were considered eligible. These were observational studies that fell into 2 groups; 9 were seeking to establish a surgical cause for TMD. Of these, only 2 of a series of 3 claimed that there was a significant link, but this claim was based on weak data (health insurance records) and was abandoned in a subsequent report. Twenty-three studies were seeking to achieve relief by orthognathic surgical intervention. These were also negative overall, with 7 articles showing varying degrees of mostly nonsignificant improvement, whereas 16 showed no change or a worse outcome. No published report on the putative effect of implant insertion was found. CONCLUSION: These apparently contradictory approaches underline a belief that oral surgical trauma or gross malocclusion has a causative role in the onset of TMD. However, there was no overall evidence of a surgical causal etiology or orthognathic therapeutic value. This review emphasizes that it is in the patients' best interest to carry out prospective appropriately controlled randomized trials to clarify the situation.

The effect of ultrasound on angiogenesis: an in vivo study using the chick chorioallantoic membrane.

PURPOSE: Ultrasound therapy induces clinical healing of irradiated avascular mandibular bone and fractures. In vitro ultrasound in tissue culture has been shown to stimulate bone formation synthesis and bone remodeling factors and to stimulate osteoblast proliferation. Therefore, the aim of the present study was to investigate the effect of short-wave (1-MHz) and long-wave (45-kHz) ultrasound on the vascularity of the chorioallantoic membrane (CAM) of a fertilized egg. MATERIALS AND METHODS: The nature of the angiogenic effect was investigated using the CAM of a fertilized egg by: (1) application of sonicated fibroblast media incorporated into methylcellulose disks onto the CAM and (2) direct application of the ultrasound, using both long-wave (45-kHz) and short-wave (1-MHz) frequencies at a range of intensities, to the surface of the egg. Angiogenesis was assessed quantitatively by three independent observers. RESULTS: Both ultrasound methods showed evidence of an angiogenic effect compared to controls. The most effective results were seen with direct application of a 45-kHz wave at an intensity of 15 mW/cm(2) and indirect application of the media of fibroblasts ultrasonicated at 1 MHz with an intensity of 0.4 W/cm(2). CONCLUSION: This model confirms that ultrasound can induce neoangiogenesis in vivo.

Demographic features of patients with concomitant facial fractures and closed head injuries in Maricopa, Arizona.

OBJECTIVE: The aim of this study was to investigate the demographic profile of Native American patients with concomitant facial fractures and closed head injuries (CHIs) and to explore the validation of the craniofacial crumple zone. STUDY DESIGN: This was a retrospective, observational, case-control study of 2131 maxillofacial fractures from 2010 to 2014, of which 173 (8%) had concomitant CHIs. RESULTS: Of the study patients, 133 (77%) were males (mean age 40.6 years). Only 2.1% of the local population was Native American, but this group represented 24% of the patients with CHIs and sustained 4.6 times more (P value < .001) assault injuries and 2.6 times more concussion (P value < .001) compared with other groups. Other trauma comparisons were not significant. Of the 173 study patients, 86 (50%), had blood alcohol levels which exceeded 80 mg/100 mL compared with 93% of the Native Americans. CONCLUSIONS: Native American patients had a highly significant predisposition to violence and road traffic accidents resulting in maxillofacial fractures and CHIs. The high blood alcohol levels found in this group also reflected longstanding serious sociologic problems. This study provides a useful model to investigate the relative ethnic/racial role of comminuted paranasal structures for the protection of the brain (i.e., the crumple zone).

Long wave ultrasound may enhance bone regeneration by altering OPG/RANKL ratio in human osteoblast-like cells.

Human osteoblast cell line (MG63) cells were treated with long wave (45 kHz, intensity 30 mW/cm(2)) continuous ultrasound (US) for 5 min and incubated for various time periods following the treatment. The reverse transcriptase polymerase chain reaction (RT-PCR) technique was used for observing the genetic expression and real-time PCR for quantitative analysis of receptor activator of NF-kappaB ligand (RANKL) and osteoprotegerin (OPG) along with alkaline phosphatase (ALP), an early bone marker, and osteocalcin (OCN) a late marker. ELISA was performed to estimate the amount of the cytokine released into the culture media. The osteoblasts responded to US by significantly upregulating both the OPG mRNA and protein levels. There was no RANKL mRNA expression observed in both the US and control groups and the protein levels were also very low in both groups. There was also no TNF-alpha expression and the TNF-alpha protein levels were insignificant. ALP and OCN mRNA were significantly upregulated in the US group. To our knowledge, this is the first study that shows the effect of US on OPG, RANKL and TNF-alpha expression. US appears to upregulate OPG and may downregulate RANKL production. From these findings, we conclude that therapeutic ultrasound may increase bone regeneration by altering the OPG/RANKL ratio in the bone microenvironment.

Reduction of postoperative pain and swelling by ultrasound treatment: a placebo effect.

Ultrasound (US) therapy is used to reduce pain and inflammation and to accelerate healing after soft tissue injury. However, there is little objective evidence of its effectiveness and the mechanisms which may cause these effects are unknown. In a placebo-controlled double-blind clinical trial we examined the contribution of placebo and massage effects in ultrasound therapy following bilateral surgical extraction of lower third molars. Four to 6 h after surgery the patients (25 per group) received either no therapy, US (0.1 W/cm2), 'mock' US with massage, 'mock' US without massage, or 'self-massage' with a dummy applicator. Facial swelling, trismus, serum C-reactive protein, serum cortisol, pain and anxiety were measured 24 h postoperatively. The results showed that the beneficial analgesic and anti-inflammatory effects of US therapy were placebo-mediated, with maximum effect in the placebo ('mock' US) group without circular massaging with the applicator). Self-massage by the patient produced no significant effect. This placebo action was independent of changes in serum cortisol or patient anxiety state. US therapy can significantly reduce postoperative morbidity, but by placebo-mediated mechanisms which are unrelated to the US itself.

Tyramine conjugation deficit in patients with chronic idiopathic temporomandibular joint and orofacial pain.

This study was carried out to explore the value of the tyramine conjugation test, an established trait marker for 'endogenous unipolar depression', in patients with chronic idiopathic temporomandibular joint and orofacial pain. Our results show that the pain patients excrete significantly lower amounts of tyramine sulphate than controls (P < 0.0004). Psychiatric assessment by the structured clinical interview for the diagnosis of mental disorders according to DSM-III-R revealed that 48% of the patients had a history of depression and 10% were currently depressed. However, the never-depressed group of patients had the lowest tyramine sulphate excretion values. These findings suggest that a common biological abnormality underlies the pathogenesis of both chronic idiopathic facial pain and depression.

A novel, de novo germline TP53 mutation in a rare presentation of the Li-Fraumeni syndrome in the maxilla.

We undertook the genetic analysis of a classic Li-Fraumeni syndrome (LFS) family with clustering of primary tumours including two maxillary sarcomas, a rare LFS site of tumour occurrence. Our aim was to investigate the presence of a specific type of TP53 mutation that could be associated with this unusual predilection of site for cancer occurrence. Mutational screening of the coding region of TP53 revealed an A>T transversion in codon 144 of exon 5 (CAG>CTG, Gln>Leu) in the germline of one of the three affected members, with loss of heterozygosity (LOH) in the tumour tissue. All other affected members were negative for germline or somatic TP53 mutations. TP53 immunohistochemistry was uninformative. The mutation we report is a de novo constitutional TP53 mutation that has not been previously described in the literature. It could explain the more burdened phenotype of the affected patient (died at 21 months). Alternative mechanisms to explain the overall family phenotype are discussed.

Antibiotic prophylaxis for orthognathic surgery: a prospective, randomised clinical trial.

A prospective, randomised, placebo-controlled double-blind clinical trial, compared short-term (1 day) and long-term (5 days) antibiotic prophylaxis after orthognathic surgery. Thirty four patients had single jaw or bimaxillary osteotomies and were given two perioperative doses of amoxycillin. Patients were then randomised to receive either placebo or amoxycillin for 5 days in a double-blind manner. Postoperatively the patients were monitored for infection by scoring a series of validated measurements of infection. In the postoperative period four patients required additional antibiotics in the short-term group and two in the long-term group (P = 0.67). Morbidity scores were higher in the short-term group, at 406 to 264 (P = 0.04), and when individual variables were compared there was a significant difference in the degree of swelling (P = 0.04). Although a 5-day regimen of antibiotic prophylaxis in orthognathic surgery did not decrease the incidence of postoperative infection significantly, it may decrease the morbidity of the operation.

Osteoradionecrosis of the jaws--a current overview--part 1: Physiopathology and risk and predisposing factors.

PURPOSE: The aim of this paper is to explore the current theories about definition, classification, incidence and physiopathology of osteoradionecrosis (ORN) of the jaws. Moreover, it is discussed the predisposing and risk factors for the development of osteoradionecrosis based on the literature review. DISCUSSION: Osteoradionecrosis is one of the most serious oral complications of head and neck cancer treatment. Osteoradionecrosis is a severe delayed radiation-induced injury, characterised by bone tissue necrosis and failure to heal. Osteoradionecrosis either stabilises or gradually worsens and is notoriously difficult to manage. The most widely accepted theory to explain its cause until recently was the theory of hypoxia, hypovascularity and hypocellularity. A new theory for the pathogenesis of osteoradionecrosis was proposed. The clinical presentations of osteoradionecrosis are pain, drainage and fistulation of the mucosa or skin that is related to exposed bone in an area that has been irradiated. The tumour size and location, radiation dose, local trauma, dental extractions, infection, immune defects and malnutrition can predispose its development. CONCLUSIONS: A better understanding of risk factors for the development ORN and of the underlying pathophysiology may improve our ability to prevent this complication and help to improve the prognosis for those being treated for osteoradionecrosis.

Osteoradionecrosis of the jaws--a current overview--Part 2: dental management and therapeutic options for treatment.

PURPOSE: The aim of this paper is to explore the current theories about pretreatment assessment and dental management of patients receiving head and neck radiotherapy, and the therapeutic options to treat osteoradionecrosis of the jaws, based on the literature review. DISCUSSION: Osteoradionecrosis is one of the most serious oral complications of head and neck cancer treatment. Osteoradionecrosis is a severe delayed radiation-induced injury, characterized by bone tissue necrosis and failure to heal. Osteoradionecrosis either stabilizes or gradually worsens and is notoriously difficult to manage. Because most cases occur in patients who were dentulous in the mandible at tumor onset, proper dental management is the single most important factor in prevention. CONCLUSIONS: Complete dental clearance before treatment is no longer necessary. Controversy exists regarding the management of osteoradionecrosis of the maxillofacial skeleton because of the variability of this condition. The treatment of osteoradionecrosis has included local wound care, antibiotic therapy, surgical procedures, and the administration of hyperbaric oxygenation. Recently, new methods of treatment were introduced, according to the new theory about its pathophysiology.

Dor facial idiopatica (2 parte): tratamento e prognostico / Idiopathic facial pain (part 2): treatment and prognosis

O presente trabalho procura introduzir um novo conceito na fisiopatologia e tratamento da chamada "sindrome da dor e disfuncao da ATM". Este trabalho doi dividido em duas partes, a primeira abrangeu a definicao, classificacao, etiologia e hipotese sobre a dor facial idiopatica v. 53(4). Nesta segunda parte abordamos o tratamento, prognostico e sugestoes de conduta. O tratamento da dor facial atipica consiste basicamente em aconselhamento e orientacao do paciente, e num segundo estagio, no uso de medicacao anti depressiva triciclica ou similar. O uso de placas de mordida e eventualmente considerado, porem tem sido pouco eficaz no tratamento. Artroscopia pode ser utilizada em pacientes resistentes e a cirurgia praticamente esta contra-indicada. Esta conduta e baseada num modelo de trabalho desenvolvido neste departamento e em outros centros mundiais, e vem revolucionando o tratamento clinico dos pacientes portadores de dor facial idiopatica

Dor facial idiopatica, parte 1: definicao, classificacao e etiologia / Idiopathic facial pain, part 1: definition, classification and aetiology

O presente trabalho procura introduzir um novo conceito na fisiopatologia e tratamento da chamada 'sindrome da dor e disfuncao da ATM'. Este trabalho foi dividido em duas partes, nesta primeira abordamos a definicao, classificacao, etiologia e hipotese sobre a dor facial idiopatica. A segunda parte abordara o tratamento e seus problemas, prognostico e sugestoes de conduta. Sob esta nova visao, esta 'sindrome' passa a ser abordada como parte da entitulada 'Dor Facial Idiopatica'. A dor facial idiopatica e subdividida didaticamente em (1) artromialgia facial, (2) dor facial atipica, (3) odontalgia atipica, (4) disestesia bucal. Sob este enfoque, fatores etiologicos oclusais sao menos valorizados, enfatizando-se mais os aspectos psicologicos e bioquimicos. O diagnostico deve ser preciso, e uma anamnese que inclua aspectos psicologicos e sociais e fundamental. Esta conduta e baseada num modelo de trabalho desenvolvido neste departamento e em outros centros mundiais, e vem revolucionando o tratamento clinico dos pacientes portadores de dor facial idiopatica