Herpes simplex encephalitis is a potentially fatal infection of central nervous system that typically involves frontal and temporal lobes. Occasionally, it presents an extratemporal involvement and in rarer cases, it is limited to the brainstem. We describe a case of an adolescent who presented with fever, sore throat, and vertigo. Clinical picture evolved to lethargy, tetraparesis, consciousness impairment, and respiratory failure. MRI showed lesions restricted to the brainstem. PCR of CSF was positive for herpes simplex type 1. Herpes virus encephalitis (HSE) is one of the most severe infections of central nervous system. It is estimated to occur in 1/250000 to 1/500000 people per year, with children and adolescents accounting for one third of all cases [Herpes simplex virus (HSV) is an ubiquitous human pathogen which can equally affect both sexes at any age . HSV-1 iThe identification of HSV by polymerase chain reaction (PCR) to detect virus DNA in cerebrospinal fluid (CSF) has become the diagnostic test of choice with a high sensitivity and specificity , 4–7. HoWe report a case of HSV-1 encephalitis, in which CNS lesions evident on MRI were restricted to the brainstem.A 14-year-old male patient presented fever and sore throat five days prior to admission, followed by vertigo, nausea, and vomiting three days later. He was previously healthy, and there was no history of drug intake. On admission, he presented hyperemia in oropharynx and vesicles on upper lip. On neurological examination, lethargy, gait unsteadiness, nystagmus, and absence of vomiting reflex were observed. Therapy with 30 mg/kg/day of acyclovir and 4 g/day of ceftriaxone was performed. Despite the treatment, this patient evolved to tetraparesis, pyramidal signs, and consciousness impairment. Two days after admission, he went into respiratory failure and coma and required tracheal intubation. Conventional MRI was performed on a Magnetom Sonata Maestro Class 1,5 T scanner from Siemens using a parallel imaging head coil. The imaging protocol consisted of T1-weighted , T2-weighted , fluid-attenuated inversion recovery (FLAIR) , diffusion-weighted MR imaging , and apparent diffusion coefficient (ADC) maps .FLAIR MR images showed symmetric abnormal hyperintensity in inferior, middle, and superior cerebellar peduncles . Axial d3 with 89% lymphocytes, 8% monocytes, and 3% neutrophiles; glucose 86 mg/dL and protein 57 mg/dL. PCR amplification in CSF was positive for HSV-1 DNA. Investigation for immunodeficiencies was performed with negative results. CSF analysis showed 42 cells/mmThe patient presented many episodes of apnea and bradypnea and was successfully extubated 1 month later. Acyclovir was administered for 21 days, and rehabilitation with physiotherapy and speech therapy was provided during hospitalization. After 45 days, he was discharged with mild dysarthria and nystagmus.The hospital ethic committee approved this case report, and parents gave informed consent for publication.In this paper we describe a rare presentation of HSV-1 encephalitis in an immunocompetent pediatric patient. In the literature, there are few reports of this kind of infection with exclusive involvement of the brainstem. Extratemporal involvement in HSV encephalitis is not rare. In a recent study, 88 patients with HSV encephalitis were evaluated, and extratemporal lesions were present in 55% of them. However, it is interesting to note that in only 3 cases there was not an associated involvement of temporal lobes [Miura et al. published a case with very similar image in a 53-year-old man probably secondary to a reactivation of HSV infection in the region of trigeminal nerve, not confirmed with positive HSV PCR . As in oThe gold standard to confirm HSV encephalitis is the detection of HSV DNA by PCR with an estimated sensitivity of 96% and specificity of 99% for early diagnosis in the general population. However, some studies have shown an increasing number of case reports with false negative PCR results, particularly in children, in which HSV PCR sensitivity can reach only 70%–75%. This fact could be related to the absence of HSV or the presence of a very low viral load in the CSF at the onset of an acute encephalitic process in children, maybe due to the presence of heme and other inhibitors [If given early in the clinical course of HSE, acyclovir reduces both mortality and morbidity in treated patients. It should be administered at a dosage of 10 mg/kg every 8 hours (30 mg/kg/d) for a period of 14 to 21 days .Radiologically, it is important to remind as differential diagnosis postinfectious brainstem encephalitis, demyelinating disorders, brain tumors, infarcts, and metabolic diseases, such as mitochondriopathies . In this


An adult Caucasian male with excruciating pains following multiple traumas was monitored, daily, over one year while managing chronic pain by self-administering quantifiable amounts of natural cannabis. Tetrahydrocannabinol, Cannabidiol, and Cannabinol were all measured in tinctures, capsules, smoke-able product plus some baked goods, prior to their administration. By allowing standardization, the subject was able to develop a daily regimen of pain management that was resistant to a battery of most patent analgesics. The chronic pain resulting from a severe on-the-job injury is a frustrating experience both for the patient as well as the treating physician and leads to chronic dependence on opiate painkillers and anti-depressants. However the relief of pain may be less desired if quality of life of such individuals is poor. The physician and the patients are left with no option but to resort to alternative modes of therapy. Cannabis has been documented to be one of such measures, especially in advanced cases of cancer . It holdThe volunteer, a 33 year old Caucasian male, volunteer was selected from the membership based on his record keeping ability, the severity of his injury, plus his daily presence at the Society, allowing continuous monitoring. The subject kept detailed notes of his condition, including pain charts, medications and dietary habits, allowing comparison by study observers. The individual's note taking allowed an in depth review of his condition. The case described here is strikingly similar to four others of its type, run over the same year, with comparable observations and outcome.Three years ago the subject  was in good health and employed as a glacier, when he fell 28 feet onto concrete. As a result of this fall he suffered multiple injuries including C6 vertebral, skull, left olecranon, left hip, ankle and trochanteric fractures with multiple disc herniations. He underwent many surgical procedures for the management of these injuries and continued with pain of levels are 5/10 on a constant basis.Cervical fracture impaired his ability of upper body to 75% and he was unable to read or work on computer. He had tension headache and tinnitus due to fractured skull. Shattered left elbow caused muscle spasms and pain at times. Left wrist pain was constant at level 8/10. It was burning at times, ice cold and had hammer like effect. Left hand was hard to use. He had back spasms 6/8 on both sides due to spine injury. He also had moderate degree of pain in left hip and ankle joints. Subsequent treatment resulted in, two years of physiotherapy, plus a long list of medications including: Arthrotec, Flexeril, ketorolac, Tylenol 3 with codeine, Naprosyn, Percocet, gabapentin, Marinol, Lyrica, Supradol, oxycodin and Oxycontin for pain. Doxepin, Imovane, Cipralex, trazadone, Elavil, Effexor XR for depression and HCTZ, Lipitor and ranitidine for a secondary hypercholesterolemia, the subject was unable to achieve satisfactory pain relief using these medications. And, he complained that the medications turned him into “a living dead person”, unable to work, go to school and carry out normal daily functions.Chromatography, using a Hewlett-Packard (Agilent) 1090 Series II binary pumping system with a 79883a diode array detector, with primary absorbance at 219 nm, was conducted. Mobile phase at 1 ml/min was isocratic with 14% aqueous (1:25:974 phosphoric acid: acetonitrile: distilled water) and 86% organic phase (acetonitrile). The column was a Zorbax C18 reverse phase 4.6 mm × 25 cm. Samples were prepared by the method modified from Health Canada for the preparation of hemp samples for HPLC analysis [The total mean concentration of cannabinoids for 30 random samples taken at the Society was; CBD plus CBD-A (5.6 ± 3.1), CBN plus CBN-A (5.1 ± 3.2) & THC plus THC-A (172 ± 26). Review of the literature of cannabinoid concentrations found throughout the world shows dramatic variation, not only of THC but the other cannabinoids and their ratios [From January of 2007 to April 2008 we monitored the cannabis use of the participant case. We accumulated data on the amount of smoke-able, encapsulated, edible and tincture preparations consumed by the member, on a daily basis. His prescription record, physician's notes, urine (drug) tests, plus daily interviews were maintained and examined. Daily cannabis use totaling 10 g of natural product cannabis, translating to an average of 420-500 mg of THC, 40-80 mg of CBD and 20-60 mg CBN, was required to achieve a sufficient degree of pain management. Significant reductions in daily pain scores as well as improved sleep, muscle spasm and general quality of life were achieved. Although, by no means pain free, the patient is now able to do some part time volunteer work, go to the gym, and lead what resembles a normal life. He consumes 10-15 g of cannabis per day. He also finds benefit in a number of supplements: for chronic pain and depression, including, GABA (500 mg), L- Tyrosine (500 mg), L-Tryptophan (550 mg), DL- Phenylalanine (500 mg) and S-adenosyl methionine (liquid) 40 drops a day. For the breakthrough pain he used cannabis tincture at 10 mg THC/drop; 2 mg CBD/drop: 15-25 drops (as needed), which relieved intense pain, in a couple of seconds. He also used Volcano (vaporizer), 2-4 g a day. Recent medical examination showed all liver functions to be normal, including clearance of the hypercholesterolemia.The analgesic properties of cannabis are becoming well established in the literature . HoweverThe case reported here represents one of many observed at the Green Cross Society. With 70% of the members treating chronic pain the same phenomenon is observed over and over that people achieve a significant degree of pain management using standardized natural product cannabis. Often a better quality of life is attained with cannabis use only, or in conjunction with reduced opiate consumption. The subject in this study is nearly one year using only natural product cannabis plus supplements for his severe pain. He recently went through yet another two surgeries to back and hand using only cannabis for post-operative pain.The roughly 4000 members of the Green Cross Society find similar benefit from standardized natural product cannabis medicine. To follow, will be publication of the Society's demographic data regarding use for various conditions such as arthritis, fybromyalgia, HIV/AIDS, and chronic pain, to name a few. A breakdown of the illnesses, what strains (cannabinoid profiles) is most effective, and at what dosages will be published at a later time.


The product of the nm23 gene has been proposed as a candidate tumour metastasis suppressor protein. A strong association has been observed between reduced expression of the nm23 gene and acquisition of metastatic behaviour in some tumour cells, including breast cancer and melanoma, but not in others, such as neuroblastoma and colon, cervical and thyroid cancers. During the early gestation period both human and murine trophoblast cells exhibit in vitro invasive properties similar to those of neoplastic cells. Such invasive properties, however, disappear in the late stage of gestation. In the present study, we examined the abundance of nm23 mRNA from various fetal-maternal interface tissues  during early (day 8), mid (day 14) and late (day 18) stages of gestation in CD1 mice, in order to determine whether nm23 plays any anti-invasive and/or biological roles during gestation. nm23 was found to be expressed in all the tissues during the early and mid stages of gestation. The expression levels were, however, variable among different tissues and development stages. In the early stage, nm23 mRNA levels were the highest and similar among tissues from the uterus, decidua, placenta and embryo. In the mid stage, the mRNA levels were reduced significantly in the uterus, decidua and placenta, but not in the embryo. In the late stage, nm23 mRNA was further reduced to the extent that it could not be seen in the decidua, was barely seen in the uterus and was weakly present in the placenta. However, the mRNA level of the embryo in the late stage was still high and similar to the early stage. We also examined nm23 expression in trophoblast cells from normal human term placenta and a highly metastatic human choriocarcinoma cell line, JAR. nm23 expression was significantly higher in JAR than in normal placenta, indicating that nm23 does not appear to have an anti-metastatic function in this cell line. Several cytokines--interleukin 2 (IL-2), tumour necrosis factor alpha  and interferon gamma (IFN-gamma)--and prostaglandin E2 (PGE2) known to modulate tumour growth and metastasis were examined to determine whether they regulate nm23 expression in JAR in vitro. The B16F10 melanoma cell line was used as control. No effect was found in the JAR cell line, whereas TNF-alpha, IFN-gamma and PGE2 down-regulated nm23 expression in the B16F10 cell line.(ABSTRACT TRUNCATED AT 400 WORDS)


The authors report the results of femoroacetabular impingement (FAI) treated with a surgical dislocation.From April 2005 to May 2007, 15 FAI hips were treated with a surgical dislocation. The male/female ratio, mean age and mean symptom duration was 12/2, 35.8 years and 2.3 years, respectively. Radiographs and MR arthrograms were taken. The clinical evaluation involved changes in the pre- and postoperative Harris hip score (HHS).There were 12 hips (80%) with at least one structural abnormality in the radiographs, with 11 (79%) labral tears and 8 (73%) abnormally high angles in the MR arthrograms. We performed 15 osteochondroplasties, 12 labral repairs, 12 acetabuloplasty, and 3 debridements. The mean HHS improved from 76 to 93 points. Three non-unions of the trochanteric osteotomy sites were encountered as complications.Radiographs and MR arthrograms are important for making a proper diagnosis of FAI and planning treatment. A surgical dislocation can be used to treat FAI but further technical improvements will be needed for fixation of the greater trochanteric osteotomy sites. Femoroacetabular impingement (FAI) is a condition that has been recently recognized to generate hip pain.7)A patient interview, physical examination, radiographs, CT scan, and MRI (MR arthrogram) are normally used to diagnose FAI.15)The treatment methods for FAI include osteotomy,In the present study the authors examined the outcomes of a surgical dislocation performed on patients with FAI.Sixteen patients (17 cases) with FAI were treated with a surgical dislocation between April 2005 and May 2007 at our hospital. Among them, 14 patients (15 cases), who were available for a clinical and radiological follow-up of more than one year, were enrolled in this study. There were 12 males (86%) and 2 females (14%) with a mean age of 35.8 years . The mean follow-up period was 2.3 years .A patient interview, physical examination, radiographs, and MR arthrogram were used to diagnose FAI. In history taking, there were no underlying diseases of the hip joint, experience of surgery, or obvious history of trauma. In the interview, the patients complained of discomfort, pain, and limited mobility during at least one of the following daily activities: sports activities, long-distance ambulation, entering and alighting vehicles, and standing up after 30 minutes of sitting.The indications for a surgical dislocation were as follows: a ≥ 1 year duration of symptoms, no response to 2-3 months of conservative treatments , and a lAll proceduresThe radiological assessment was based on the pre- and postoperative measurements of the following parameters on the anteroposterior and lateral views of the hip: the degree of arthritis, Tönnis angle, center-edge angle of Wiberg, the presence of acetabular retroversion , femur neck-shaft angle, congruity of the femoral head and acetabulum, anterior femoral head-neck off set, and the presence of an abnormality at the femoral head (bump and herniation pit). The intra-articular abnormalities and alpha angle were assessed on the MR arthrograms. Cam type impingement was defined as the presence of a bump, herniation pit, and abnormal alpha angle. Pincer type impingement was defined as that of acetabular retroversion or protrusion. The mixed type impingement contained the features of the cam and pincer types. For a clinical assessment, the changes in the values of the impingement test and HHS measured preoperatively and at the last follow-up were analyzed.The radiographic results showed a mean Tönnis angle , which indicates the overcoverage of the anterosuperior acetalubum, of 7.9° , and was abnormally high in 2 cases. The mean center-edge angle of Wiberg , which is also a measure of overcoverage of the anterosuperior acetalubum, was 35.5° , and decreased to < 20° in 1 case. In 6 cases, the cross-over and posterior wall signsIntraoperatively, a labral tear was observed in 12 cases (80%). Eleven (79%) of them were noted in the MR arthrograms. Acetabular cartilage degeneration  was noted in 7 cases (43%). Labral ossification and acetabular osteophyte formation were identified in 3 (20%). Regarding the surgical techniques, a bumpectomy, labral repair, resection of the anterior rim and debridement was performed in 15, 12, 12 and 3 cases, respectively. The mean HHS improved from 76 points  preoperatively to 93 points  at the last follow-up. The anterior impingement test was negative in all cases at the last follow-up  and 6.No complications, such as avascular necrosis of the femoral head and infection developed at the last follow-up. However, there were 3 cases of nonunion of the trochanteric osteotomy site, which were treated with internal fixation using a trochanteric plate .Wenger et al.MR arthrogram is the most reliable technique for detecting an intra-articular lesion, and allows an assessment of labral tears, labral cysts, cartilage degeneration, synovitis, and bony changes.Labral tears in FAI are usually located in the anterosuperior region (12 to 2 or 3 o'clock direction). They tend to occur at the inner aspect of the labrum similar to partial rotator cuff tears, and rarely affect the entire layer. Like the meniscus, the labrum has a nerve endings for pain perception and proprioception, and pain occurs when it is damaged or under pressure.Surgical dislocation, which is carried out with the hip in anterior dislocation, allows a large view field and easy detection of a lesion. It can be also considered as an alternative procedure in patients with FAI that is non-responsive to conservative treatment, particularly because procedures for common lesions in the anterosuperior acetabulum  can be performed and assessed by the naked eye. However, assist devices, such as a spherometer gauge,Nonunion at the trochanteric osteotomy site occurred as a complication in 3 cases (20%). This has not been reported previous studiesTo summarize, in a radiological assessment, 1 or more structural abnormalities were found in 12 cases (80%). Intraoperatively, 11 (79%) labral tears were detected on MR arthrograms. Therefore, radiographs and MR arthrogram are effective tools for diagnosis and treatment planning of patients with FAI. However, despite the satisfactory clinical outcomes of surgical dislocation, improvements in fixation methods at the trochanteric osteotomy site will be needed.


Male pattern baldness (MPB), an observable trait, has been reported to be associated with various diseases, such as prostate cancer and cardiovascular disease. Oral sulfur-containing gases have also been suggested to be useful as markers of systemic health condition. However, there are no known reports regarding the associations among MPB, and oral sulfur-containing gases, and systemic health conditions in males.We studied 170 male subjects aged either 60 or 65 years old. The degree of MPB was assessed using the Norwood-Hamilton Baldness scale. Oral sulfur-containing gases were measured using a compact-designed device. All subjects completed physical and laboratory blood examinations, a face-to-face medical questionnaire, and an oral examination.3SCH3 and baldness patterns, independent of age. When we analyzed whether the association was linked to systemic health condition, a strong significant association was observed between the level of CH3SCH3 and severe MPB in subjects with gastrointestinal diseases, hypertension, and hypercholesterolemia.There were significant differences between the levels of CH3SCH3, a sulfur-containing gas that causes oral malodor, in elderly Japanese males. Further, the association was intensified by the existence of gastrointestinal tract and metabolic disorders.These results suggest that MPB is associated with the level of CH It has been reported that for diagnosis of systemic diseases, male pattern baldness (MPB), a clearly observable trait, can be used ,2. It wa2S), methanethiol (CH3SH), and dimethylsulfide (CH3SCH3), are responsible for oral malodor [2 and methane [2S and CH3SH in breath could be explained by an extremely efficient metabolism of these gases by the colonic mucosa or liver [3SCH3 might be expected to appear in breath, and Suarez et al. (2000)[3SCH3 is derived from the gastrointestinal tract. In addition, Hoshi et al. (2002) [Helicobacter pylori-positive and negative patients, and found that the levels of H2S and CH3SCH3 in mouth air were significantly higher in positive patients. Considering that various systemic conditions affects breath in the mouth, as described above, it is possible that MPB has an association with levels of oral malodor.On the other hand, oral malodor is reported to be primarily associated with dental caries and periodontal disease, though involvement of other factors including systemic health conditions and lifestyle have not been ruled out. It is generally known that volatile sulfur-containing gases, which mainly consist of the three compounds hydrogen sulfide  suggeste. (2002)  comparedThe purpose of the present study was to investigate the severity of MPB in correlation with these sulfur-containing gases. We also investigated whether systemic health disorders were linked to changes in the levels of those gases.This cross-sectional investigation was part of a population-based study conducted to investigate the relationships between oral and systemic health. A total of 170 healthy community-dwelling male subjects aged either 60 or 65 years old residing in Fukuoka Prefecture were recruited in 2006, and all were provided an explanation of the nature of the research project and provided written informed consent. The study was also approved by the Ethics Committee of Kyushu Dental College (no.05022250).Each subject completed a questionnaire regarding lifestyle, oral and systemic health conditions, and medical history, and also underwent physical, laboratory blood, and oral examinations. All current medication usage was recorded, including treatments for hypertension, diabetes, and hyperlipidemia. Blood samples were taken after the subjects had refrained from oral intake and smoking for at least 2 h before collection, then transported to a commercial laboratory on ice for measurements.The degree of MPB was assessed in the male subjects using Norwood-Hamilton Baldness scale  by a tra2O3) semiconductor gas sensor , a compact-sized device that is popular in dental clinics in Japan, as described previously [2S, 358.7 ppb ; CH3SH, 143.0 ppb ; CH3SCH3, 19.5 ppb  [For sampling, subjects were asked to refrain from oral activity, including eating, drinking, tooth brushing, and mouthrinsing, before testing. Oral sulfur-containing gases were measured using an indium oxide . The level of statistical significance was set at 0.05 for all of the analyses.To assess differences between groups, a chi-square test was used for categorical variables and ANOVA for continuous variables, followed by adjustment for the effects of age if necessary. Linear trends for the associations were assessed by computing the 3SCH3. There were no significant differences between the ages groups regarding oral sulfur-containing gases. The mean values for H2S, CH3SH, and CH3SCH3 for all subjects were 4.64 ng/10 mL (= 346.6 ppb), 2.82 ng/10 mL (= 149.5 ppb), and 0.54 ng/10 mL (= 22.2 ppb), respectively. We also investigated the effects of systematic health on CH3SCH3 levels, as shown in Table 3SCH3 in those with severe MPB showed significant associations with gastrointestinal disease, hypercholesterolemia, and hypertension (treated) (P for trend < 0.05 for each), with gastrointestinal disease and hypercholesterolemia occurrences shown to be approximately 2 to 5-fold higher than the level shown in Table H. pylori. In addition, in subjects with other systemic diseases such as hepatic and diabetic diseases, there were no significant differences among the groups regarding CH3SCH3 levels.The prevalence and distribution of MPB in the 170 male subjects is shown in Table 3SCH3 levels in volatile sulfur-containing gases and MPB. Further, and the level of CH3SCH3 was found to be much greater in males with gastrointestinal diseases, hypertension, and hypercholesterolemia. In general, oral sulfur-containing gases have been reported to be influenced by systemic conditions [3SCH3 is the main contributor to extra-oral or blood-borne halitosis, due to a hitherto unknown metabolic disorder, while CH3SH and H2S are the main contributors to intra-oral halitosis [H. pylori infection, gastritis, and esophageal reflux disease [3SCH3 were observed in those with gastrointestinal diseases. Considering the correlations among halitosis, gastrointestinal diseases, and sebaceous gland diseases as described above, it is reasonable that a combined effect of MPB and gastrointestinal disease may lead to increased CH3SCH3.In the present cross-sectional study, we investigated community-dwelling elderly subjects and found a significant association between CHnditions , though alitosis . A non-oalitosis . The rev disease . Most re disease , though H. pylori-positive and -negative patients, and reported that levels of H2S and CH3SCH3 in mouth air were significantly higher in the positive patients. Our results also showed that levels of CH3SCH3 were lower in subjects who had received treatment to eliminate H. pylori, though the difference was below the level of significance. On the other hand, the levels of H2S were scarcely changed. Considering that H2S originates from microbial putrefaction within the oral cavity [H. pylori, which might be no greater than that of CH3SCH3. An intervention study is needed to clarify this relationship.Hoshi et al. (2002)  comparedl cavity , this fi3SCH3 levels were observed. There are no known reports regarding associations between halitosis and systemic diseases, such as hypertension and hypercholesterolemia, whereas several studies have indicated that MPB may be a risk factor for some diseases, such as CVD or prostate cancer, though the detailed mechanisms are unknown [On the other hand, in subjects with hypertension or high cholesterol, stronger associations between MPB and CH unknown . One pla unknown . A recen unknown . HoweverAnother recent report  found anThere are some limitations to our study. First, the number of subjects was limited and the results were obtained in a preliminary research manner. Further, the study subjects were generally in good health, thus our findings may indicate that an association that exists primarily in healthy elderly subjects. Finally, because all subjects were Japanese, thus our results may not be applicable to men of other racial groups.3SCH3 levels, though the causes and effects remain unclarified. Conversely, it is possible that a subject with higher levels of CH3SCH3 and severe MPB may be predisposed to gastrointestinal diseases and cardiovascular-related diseases. If so, then assessment of MPB and measurement of oral malodor, simple and non-invasive methods, may be useful as screening for potential systemic health conditions, including disorders in the gastrointestinal tract and metabolic disorder, in a large population-based examination. Nevertheless, additional research is needed to corroborate these findings and clarify the biological mechanisms related to the increase in CH3SCH3 levels in subjects with severe MPB.From this study, within the limitations of the present study, our results suggest that MPB is associated with an increased risk of oral malodor independent of age, while the existence of gastrointestinal disease, and known risk factors for CVD and CHD  were found to strengthen association between MPB and CHThe authors declare that they have no competing interests.The epidemiological study was supervised by TT and TA. TA, SA, IS, YT, AY, TH, TT, participated in the epidemiological study. TT initially designed the study. TA contributed towards analysis and interpretation of data, and wrote the first draft of the manuscript. All authors read and approved the final version of the report.The pre-publication history for this paper can be accessed here:


The long-term prognosis of patients with colon cancer is dependent on many factors. To investigate the influence of a series of clinical, laboratory and morphological variables on prognosis of colon carcinoma we conducted a retrospective analysis of our data.Ninety-two patients with colon cancer, who underwent surgical resection between January 1999 and December 2001, were analyzed. On survival analysis, demographics, clinical, laboratory and pathomorphological parameters were tested for their potential prognostic value. Furthermore, univariate and multivariate analysis of the above mentioned data were performed considering the depth of tumour invasion into the bowel wall as independent variable.On survival analysis we found that depth of tumour invasion , type of operation  and CT scanning  were predictors of survival. Considering the degree of mural invasion as independent variable, on univariate analysis, we observed that mucorrhea, anismus, hematocrit, WBC count, fibrinogen value and CT scanning were significantly related to the degree of mural invasion of the cancer. On the multivariate analysis, fibrinogen value was the most statistically significant variable (P < 0.001) with the highest F-ratio (F-ratio 5.86). Finally, in the present study, the tumour site was significantly related neither to the survival nor to the mural invasion of the tumour.The various clinical, laboratory and patho-morphological parameters showed different prognostic value for colon carcinoma. In the future, preoperative prognostic markers will probably gain relevance in order to make a proper choice between surgery, chemotherapy and radiotherapy. Nevertheless, current data do not provide sufficient evidence for preoperative stratification of high and low risk patients. Further assessments in prospective large studies are warranted. Advances in the management of colon cancer over the past decades have resulted in an improvement of the prognosis of the disease. The proportion of stage I and II has increased from 39.6% to 56.6% leading to a raise of five-year relative survival from 33% in 1970s to 55.3% in 1990s [Nevertheless, the five-year survival rate of colon cancer has not improved dramatically in the last decade, remaining at approximately 60%, and colon cancer is still one of the leading killers in the Western countries .In truth, despite curative resection, many patients develop recurrence at the primary site or distant organs. These high risk patients could be candidates for more aggressive treatments (neoadjuvant chemotherapy) in order to improve the prognosis . This taPrognostic factors derived from clinical, laboratory and pathologic data of colorectal cancer patients have been considered important and have been investigated in order to make a proper choice between surgery chemotherapy and radiotherapy, but the results of the previous studies were often intriguing and conflicting ,5.Actually, most studies investigating prognostic factors for large bowel cancers did not distinguish between the subpopulation of colon and rectal cancer, despite the different biological characteristics, treatment modalities, pattern of recurrence and survival rates of the two group of neoplasms .Further, it was suggested that proximal and distal colon cancer can differ in histopathologic characteristics, molecular pattern, stage of diagnosis and, consequently, clinical outcome. Over the past 20 years, the literature has demonstrated a stage migration of colorectal cancer from distal to proximal sites with a tendency for proximal tumours to present at a more advanced stage than distal tumours .At the moment, the most accurate prognostic factor remains the extension of the tumour into the bowel wall as expressed in the Dukes classification or TNM classification ,4.The main endpoint of the present study was to evaluate the prognostic implication of many preoperative clinical, laboratory and patho-morphological data by both univariate and multivariate analysis.Therefore, we performed two statistical analysis of clinical, laboratory and patho-morphological data in a group of patients with colon cancer, considering survival and pT staging as the independent variables.A total of 103 patients with colon cancer, who were surgically treated between January 1999 and December 2001 at the Department of General Surgery, University Hospital Tor Vergata, Rome, were evaluated for eligibility.Patients who suffered from rectal cancer, colon carcinoma with locally advanced invasion (pT4) or colon cancer with distant metastasis were excluded. Only elective surgery cases were considered. Thus, out of 103 subjects, 92 patients, who underwent to curative resection and were followed for at least 5 years, were analysed.Preoperative staging was performed using colonoscopy, conventional transabdominal ultrasonography, CT scan of abdomen, barium enema, chest X-ray and blood tests that included tumour markers.CT scanning was performed using oral and intravenous contrast. Patients were scanned at 5-mm intervals from the diaphragm through the pubic symphysis. We did not use a three-dimensional endoluminal view; we used only transverse CT images. The assessment of extracolonic compartment metastases of the abdomen and pelvis was performed on 5-mm venous phase contrast-enhanced transverse images.T2 = smooth outer border of thickened colorectal wall with a clear surrounding fat plane, T3 = tumor with rounded or nodular advancing margin, T4 = obliteration of fat planes between colorectal tumor and adjacent organs. This classification was used to address known limitations at CT in distinguishing T1 and T2 lesions.Bowel wall thickening of more than 0.5 cm was considered to indicate the presence of a neoplasm. Colorectal wall invasion was analyzed according to a modified T classification reported by Filippone et al. Contrast-enhanced CT criteria for T staging were ≤The cancer was found in the ileocecal junction of 11 patients (11.9%), in ascending colon of 14 patients (15.2%), in transverse colon of 8 subjects (8.7%), in hepatic flexure of 8 patients (8.7%), in splenic flexure of 7 patients (7.6%), in descending colon of 10 patients (10.9%) and in sigmoid colon of 34 patients .All patients were surgically treated. Right hemicolectomy was performed in 14 patients, ileocecal resection in 11 cases, transverse colon resection in 8 patients, left hemicolectomy in 25 patients, sigmoid resection in 24 patients, Hartmann procedure in 10 cases.T and N staging was based on the international TNM classification, as follows: pT1, tumor invading submucosal layer; pT2, tumor invading muscularis propria or subserosa; pT3, tumor penetrating serosa and perivisceral fat; and pT4, tumor invading adjacent organs. Lymph nodes were likewise classified: N0, no regional lymph node metastasis; N1, metastasis in one to three perirectal lymph nodes; N2, metastasis in four or more perirectal lymph nodes; and N3, metastasis in pelvic lymph nodes. The patients were classified as follows: 5 pT1 N0 M0; 2 pT1 N1 M0; 4 pT1 N2 M0; 16 pT2 N0 M0;; 2 pT2 N1 M0; 2 pT2 N2 M0; 37 pT3 N0 M0; 14 pT3 N1 M0; 10 pT3 N2 M0.Medical records of patients with colon cancer were isolated in a computerized database. The database included 53 demographics, clinical, laboratory and patho-morphological parameters: name, sex, age, symptoms and major medical problems of patients; laboratory data and neoplastic markers values; location, size, endoscopic appearance and preoperative staging of the tumour; operation type, degree of differentiation and pTNM of the cancer; postoperative course, recurrence, and condition at follow-up.These patients returned for follow-up every 6 months during the first 3 years and then once a year. When necessary, telephone contact was made with the patient to obtain up-to-date information. The dead line of follow-up was up to January 2007. The longest follow-up time was 96 months with an average period of 60 months.Statistical analysis was performed using the software program Statgraphics Plus. Analysis of variance (F-ratio) was used for comparison of quantitative parameters, whereas qualitative parameters were analyzed by Chi-square test. To compare the prognostic value of the statistically significant variables, multivariate analysis  was performed with 95% CI for the means of each variable.P values were two-tailed. P values of less than 0.05 were considered statistically significant.All Between January 1999 and December 2001, 92 patients with colon cancer underwent surgical resection at the Department of General Surgery, University Hospital Tor Vergata, Rome and were included in the study.Patients consisted of 48 males and 44 females who ranged in age from 37 to 94 years (average age of 69.2 years). The average interval between symptoms and diagnosis was 5.4 months (range 1–70).In our experience 92 patients with colon cancer were recruited between January 1999 and December 2001 and followed up to December 2006. The average follow up period of the 92 patients was 40.6 months (range 3–96). The 5-year survival rate was 39.1% (36/92).The results of univariate analyses of clinical, laboratory and pathomorphologic data considering pT staging as the independent variable are summarized in table 3 and fibrinogen value > 400 mg/dl were significantly related to pT staging > 2. Further the degree of CT scan T-staging were significantly related to pT staging of the tumour.Presence of mucorrhea and anismus, hematocrit value ranging between 16,7% and 31%, WBC count between 4500 and 5800/mm3  or hematocrit value of 16,7–31% . Furthermore, CT scan-T staging appeared strongly related to the pathologic-T staging .Among clinical parameters, presence of mucorrhea  appeared more significantly related to pT staging > 2 than anismus . Among laboratory data, fibrinogen value > 400 mg/dl  appeared more significantly related to pT > 2 than WBC count ranging between 4500 and 5800/mmOnly those variables that appeared significant in the univariate analysis were considered for the multivariable analysis. Fibrinogen value appeared the most significant predictor of pathologic-T staging of the tumour , as shown in table On survival analyses, the pathologic-T staging of the tumour , the operation type  and the CT scanning  appeared to be prognostic indicators , the duration of therapy and whether there is a real possibility of stratifying patients for neoadjuvant treatment on the basis of preoperative prognostic factors -25.Actually, recent studies, that underlined remission rates as high as 40% in advanced colon cancer and the efficacy of adjuvant chemotherapy, are now leading to revaluation of the therapeutic approach to colon cancer. Data from animal models and tumour biologic hypotheses also point to a possible advantage for preoperative therapy to improve disease-free survival and overall survival in colon cancer patients .Therefore, the main target of this investigation was to identify preoperative clinical, laboratory and patho-morphological parameters that may be indicators of the pT staging of the tumour.3 were significantly associated to pT > 2. Further fibrinogen value > 400 mg/dl both on univariate and multivariate analysis was significantly associated to pT staging > 2; however the importance of fibrinogen value to predict tumour invasion and prognosis of these patients remains uncertain, given that this marker is not specific and it is also involved in acute-phase reaction.Considering clinical data, we observed that the presence of mucorrhea and anismus were indicators of pT staging > 2, it was suggested that these signs are also related to the tumour size. On laboratory, we found that hematocrit value between 16,7 and 31% and WBC count ranging between 4500 and 5800/mmThe significance of increase of CEA and CA 19-9 levels to predict the prognosis of the patients remains a problem for debate; in our experience CEA and CA 19-9 levels were found indicators neither of pT staging nor of survival. Differently, in a recent study on 103 patients with colorectal carcinoma, Nozoe et al  observedBesides this, an interesting result of our investigation is the importance of CT scan preoperative staging both as predictors of survival and of pT staging. These data confirm the diagnostic accuracy of this tool not only for the rectum but also for the colon cancer as pointed out by Blomqvist in a recent review on advances in preoperative staging of colorectal cancer patients. The author underlines the technological advancement of CT scan related to hardware, software, development of CT colonography, new contrast enhancement agents ,29.In summary, these data confirm the vital importance of tumour stage in predicting survival and recurrence and provide the grounds for further work in order to assess the prognostic significance of various clinical, laboratory, patho-morphological markers and to define the subgroups of patients at different risk of recurrence who could be treated more or less intensively.The authors declare that they have no competing interests.MG: manuscript preparation and critical review. GM: critical review. GMG: data collection and manuscript preparation. FC: literature review and manuscript preparation. MGM: literature review. CN: data collection and literature review. FR: critical review. AMF: critical review. All authors read and approved the final manuscript.


Acinetobacter, but differed in their cellular morphology and cellular fatty acid profile. We report here on NO-1's clinical and epidemiologic significance. In all cases, isolates were recovered from an animal bite wound; 17 (77%) were isolated from a dog bite wound, 4 (18%) from a cat bite wound, and one (5%) from an unspecified animal bite. Clinical data were retrieved and reviewed for 12 (55%) of the 22 bite victims. None of the patients had pre-existing conditions associated with immunosuppression. Seven (58%) patients were hospitalized for a median stay of 5 days . The median time between bite to the worsening of symptoms was 17.5 hours . All patients recovered following antibiotic treatment.From 1974 to 1998, 22 isolates of an unusual bacterium, designated as CDC group nonoxidizer 1 (NO-1), were sent to the Centers for Disease Control and Prevention for identification. The organism's phenotypic characteristics were similar to asaccharolytic strains of  The isolate was a unique, fastidious, non-oxidative, gram-negative rod and was named nonoxidizer group 1 (NO-1). From 1974 to 1998, the SBRL identified 21 additional isolates received from state and local hospital laboratories across the United States and Canada. The biochemical and phenotypic characteristics of the organism have been described elsewhere Inclusion was limited to those patients from whom isolates sent to SBRL were identified as NO-1 between 1974 and 1998. In collaboration with state and territorial public health epidemiologists and hospital infection control practitioners, we gathered relevant clinical records and exposure data to determine the clinical significance of and risk factors for NO-1 infection. State epidemiologists, hospital infection control practitioners, or both were notified of cases that occurred in their state or hospital and were requested to submit clinical records for each case, including chart notes, discharge summaries, and clinical laboratory results. Using a standardized form, we abstracted clinical data for each patient. Information recorded included demographic characteristics, signs and symptoms of illness, treatment, laboratory results, and outcome. We collected information on symptoms including erythema, swelling, drainage, cellulitis, loss of motion, and any other symptoms that treating physicians noted.This protocol was determined to be exempt from human subjects review requirements because the gathering of clinical information to accompany strains was a standard part of reference diagnostic submission, and, therefore, considered surveillance activity for a newly emerging pathogen. No specific research question was investigated.Data were entered and analyzed with Epi Info version 6.04 . Continuous variables were evaluated by using the Kruskal-Wallis test, and categorical variables were compared using the chi-square test or Fisher’s exact methods.Of the 22 patients from whom NO-1 isolates were recovered, 11 (50%) were male with a median age of 22 years . The median age of males was significantly different from that of females . In all 22 cases, the organism was isolated from an animal bite wound site: 17 (77%) from a dog bite wound, 4 (18%) from a cat bite wound, and 1 (5%) with no recorded bite source. Fourteen (64%) isolates came from bites on the extremities, 6 (27%) came from face or neck wounds, and for 2 (9%) no anatomic site was specified.3. Hematocrit (range 36% to 43%) and platelet counts (range 140 to 331 K/mm3) were normal. Laboratory reports on cultures from wound specimens are summarized in Weeksella zoohelcum, Eikenellla corrodens, Pasteurella multocida, Staphylococcus aureus, and Corynebacterium spp., coagulase-negative Staphylococci, and unidentified gram-positive cocci and enteric gram-negative rods. None of the NO-1 isolates were identified by the original hospital laboratory.We were unable to retrieve 10 (45%) of the 22 medical records for reasons including 1) records were lost, destroyed by accident or natural occurrence, or archived off-site, or 2) a patient was seen in the emergency room and notations were not in the patient record. The 12 patients whose records were available for review are summarized in No data were available on the depth of the wounds. Standard cleansing, including irrigation and debridement of wounds followed by dressing, was documented for 8 of 12 patients. Five of the 12 patients had wound closure by suture after irrigation. No associations were seen between suture therapy and severity of symptoms or duration of recovery.Seven (58%) persons were hospitalized for treatment, 5 (42%) were managed as outpatients . All 12 A history of asthmatic bronchitis and respiratory allergies, arthritis, and a ventricular septal defect was noted for Cases 6, 4, and 9, respectively. Two patients were elderly (>60 years). No pre-existing conditions or illnesses were documented for the rest of the patients.NO-1 is a recently identified bacterium associated with dog and cat bite wounds. Infections in which NO-1 bacteria were isolated appear to be local . Following receipt of a bite wound, NO-1 infections, without severe disease, can occur in healthy persons with no underlying illness. The most common clinical features associated with NO-1 infections included purulent drainage, increased pain with erythema and swelling, and cellulitis, which are clinically similar to features of infections caused by other animal bite-related organisms Acinetobacter species Acinetobacter species (. Studies are under way at the SBRL to determine the taxonomic classification of NO-1.As described by Hollis, et al., the phenotypic characteristics of NO-1 are similar to those observed with asaccharolytic The patients from whom NO-1 were isolated were successfully treated with a variety of antibiotics. In general, intravenous antibiotics my have an advantage over oral antibiotics in preventing bacterial infections associated with bite wounds, including those caused by NO-1, because of more rapid delivery of drug to affected tissues ,,,,Most dog and cat bite wounds in young children occur on the face, head, and neck; by contrast, the extremities tend to be injured in young adults and adults (Staphylococcus spp., Streptococcus spp., Corynebacterium spp., anaerobes, and Pasteurella multocida, NO-1 should be considered in the differential diagnosis of infected bite wounds from cats and dogs. Group NO-1 organisms have been shown to be similar to two isolates from oral and nasal fluids from dogs called “unidentifiable species no. 4” by Bailie et al. In addition to other pathogens that are associated with bite wounds, such as At present no surveillance system exists for reporting dog or cat bite wound-associated infections and, therefore, the incidence of NO-1 isolated from bite wound infections is not known; however, these 22 reported cases likely represent only a fraction of the true number of potential NO-1 infections. Several of the case records noted the gram-negative rods as possible exogenous contaminants; thus, many more NO-1 infections may be unrecognized and undocumented. The etiologic role and the pathogenicity of NO-1 are unclear. Enhanced awareness of this organism by physicians will improve our understanding of this new zoonotic infection and clarify its clinical significance. With over 4 million animal bites occurring in the United States each year, bacteria associated with dog and cat bite wounds, including NO-1, are an important public health problem.


Numerous studies were performed to illuminate mechanisms of tumorigenesis and metastases from gene expression profiles of Head and Neck Squamous Cell Carcinoma (HNSCC). The objective of this review is to conduct a network-based meta-analysis to identify the underlying biological signatures of the HNSCC transcriptome.Pre, premalignant lesions v.s. normal; TvN, primary tumors v.s. normal; and Meta, metastatic or invasive v.s. primary tumors. Reported genes extracted from the literature were systematically analyzed. Participation of differential gene activities across three progressive stages deciphered the evolving nature of HNSCC. In total, 1442 genes were verified, i.e. reported at least twice, with ECM1, EMP1, CXCL10 and POSTN shown to be highly reported across all three stages. Knowledge-based networks of the HNSCC transcriptome were constructed, demonstrating integrin signaling and antigen presentation pathways as highly enriched. Notably, functional estimates derived from topological characteristics of integrin signaling networks identified such important genes as ITGA3 and ITGA5, which were supported by findings of invasiveness in vitroPre, TvN, and Meta stages, respectively. Results highlighted chromosomal regions of 6p21, 19p13 and 19q13, where genomic alterations were shown to be correlated with the nodal status of HNSCC We included 63 HNSCC transcriptomic studies into three specific categories of comparisons: Pre, TvN, and Meta, respectively.By means of a systems-biology approach via network-based meta-analyses, we provided a deeper insight into the evolving nature of the HNSCC transcriptome. Enriched canonical signaling pathways, hot-spots of transcriptional profiles across the genome, as well as topologically significant genes derived from network analyses were highlighted for each of the three progressive stages,  Head and Neck Squamous Cell Carcinoma (HNSCC), ranked the 6th common cancer worldwide, has long been recognized with a heterogeneous clinical presentation and a poor prognosis in advanced stages Recent advance in using microarray technology to investigate HNSCC cancer biology has attracted significant research interest. Choi and colleagues Graphical presentations of biological networks become a common platform to demonstrate gene–gene interplays and to model human diseases at systems-level Pre, premalignant lesions v.s. normal; TvN, primary tumors v.s. normal; and Meta, disseminated  v.s. primary localized tumors. Results in the original articles were demonstrated to identify patterns of etiologic or metastatic processes of HNSCC in terms of Pre, TvN, or Meta. Here, we synthesized results of differential gene expression profiles into knowledge-based interacting networks. It was designated that the evolving nature of HNSCC could be read out from the topological characteristics, the prismatic visualization of three staged interacting networks, and the probabilities of reporting differential gene activities across the genome.We recently developed a knowledge-based network approach to conduct genomic meta-analysis of HNSCC Pre, premalignant lesions v.s. normal (n = 5); TvN, primary tumors v.s. normal (n = 41); and Meta, disseminated  v.s. primary localized tumors (n = 26). We conducted this meta-analysis in accordance with the standard protocol recommended by the Quality of Reporting of Meta-analyses group For each study, reported genes were extracted from tables, text or supplements. We converted various kinds of gene or sequence identifiers, such as UniGene cluster IDs, Genbank accession numbers, gene symbols, or Affymetrix probe sets, into the universal Entrez GeneIDs. GeneIDs conversion was done by the web-based program of DAVID2007–2008  θ, were reported, the standardized bounded fold changes would be |θ′| = θ/(maximum of θ) with regard to up- and down-regulated genes separately; alternatively, if only directions of up- or down-regulation were reported, the bounded fold changes would be translated into 1 for up and −1 for down, respectively. For each of the Pre, TvN or Meta stages, consensus of gene expression was computed as the averaged mean of the bounded fold changes if studies reported values of fold changes; else, the median was computed instead if at least one study reported only directions of gene regulation. Genes without such information were coded with 0 as the bounded fold changes in the analysis.In order to synthesize the original information of fold changes, a novel method was developed to overcome differences in multiple microarray platforms. This method based on the assumption that different transcriptional measurements of the same target gene, i.e. different sequence or gene identifiers converted into the same Entrez GeneID, were indeed representing the same functional entity. For each study, if fold changes, TvN and Meta was tested through comparisons of ratios of internal consistency, defining as the percentage of verified genes for each study within the groups of interest, i.e. studies of lesions in different subsites, studies using different microarray platforms, studies investigating different endpoints, or the proposed classification. Classifying studies in TvN or Meta would be considered reasonable if the ratios of consistency were higher than those within the subgroups of interest. For instance, of the 121 differentially expressed genes by Ibrahim and colleagues, 74 genes (61%) were verified when classified in TvN; 38 genes (32%) verified among the 23 studies using cDNA microarrays in TvN; as well as 32 genes (27%) verified among the 19 studies examining tumors located exclusively in the oral cavity.Owing to the underlying heterogeneity among included studies, such as differences in the tumor of origins , multiple microarray platforms, different analytical approaches taken, and diverse endpoints, we sought to examine the validity of three staged classification of the HNSCC transcriptome. First, we systematically computed the frequency of reporting the same Entrez GeneID within each stage of comparison. If a gene was reported more than once, this gene was regarded as verified. Subsequently, the validity of Pre, TvN, and Meta, were imported into the Ingenuity Pathways Analysis (IPA) Software  to obtain six sets of networks for further analyses. We used IPA to identify the top 10 enriched canonical pathways for each stage of comparison  were included in the analysis.Networks generated from the IPA consisted of identified focus genes from the user input and other correlated molecules or genes from the knowledge base i was disrupted, i.e. removed in the interacting network, we estimated the potential for pathophysiological perturbation by the informational score i(f), computed by the number of blocked out paths divided by the number of breaking down components. The informational score (if) was calculated as equation (1), where m denoted the number of broken-down components after removing a node i, Ncp denoted the total number of nodes in this component where node i was located, S was the size of each broken-down component, and m.lg was the iterating counter part for each S to calculate the blocked-out paths.Based on findings in model organisms, indicating that network structure such as dynamic modularity Sub-networks of enriched canonical pathways were extracted from each of the three progressive stages of the HNSCC transcriptome for independent topological analyses . PromineTvN comparison consisted of 41 papers, the cumulative probability of a cytoband with k genes reported would be g was the number of articles reporting gene g in TvN. In order to compare across three progressive stages, we standardized PB of the Pre, TvN, and Meta to be within 0∼1 by dividing the maximum probability of each stage. We plotted PBs of three progressive stages along the chromosomal coordinates to identify hot-spot regions. For the identified hot-spots, differential gene activities (bounded fold changes) were illustrated on the resolution of a single gene for each stage of comparison.Across the genome, we computed the accumulative probabilities (PB) of reporting genes within the chromosomal segments for each stage of comparisons. For instance, in the Pre, TvN, and Meta comparisons. Eighty-two genes out of 1822, 1260 out of 4311, and 321 out of 2293 were found reported at least twice in the Pre, TvN, and Meta comparisons. With regard to the direction of fold changes of the verified genes, we found the least contradiction in TvN (217/1260 = 17.2%), less in Meta (117/321 = 36.5%), and the most, in Pre (42/82 = 51.2%). There were few genes overlapped between Pre and Meta, whereas many overlapped between any other pairs of comparisons. In TvN with a bounded fold change of 1, was found consistently highly up-regulated, albeit that tumors were harvested from different anatomical subsites; whereas in the Meta comparison, we found MMP1 with three studies reporting induced Meta might stem from differences in prognostic endpoints investigated rather than the lesion sites.There were 1822, 4311, and 2293 genes, respectively, reported from 5, 41, and 26 papers in the TvN (mean ratio = 71%), secondly in Meta (31%), and lastly in Pre (26%)  or tumors from unspecified locations (mix). Nineteen papers procured specimens located exclusively within the oral cavity. Unexpectedly, we found a significant decrease of the internal consistency within this subgroup (mean ratio = 37%). Gene lists reported from distinct anatomical subsites were examined in details  . In TvN, details . The majMeta, we classified studies into 4 subgroups . Similar to the results in TvN, ratios of internal consistencies within each subgroup dropped significantly, especially in the dM and surv group . Overall, we believed that classification of three progressive stages, Pre, TvN and Meta, of the HNSCC transcriptome was sufficient for the purpose of this meta-analysis.With regard to differences of prognostic outcomes investigated in Pre, TvN, and Meta were first imported into IPA to obtain six sets of networks. We compared these two levels of analyses to come up a consensus of the enriched signaling pathways. The interacting networks of the HNSCC transcriptome were ultimately built on those generated by the full gene lists. Networks of scoring higher than 10  were parsed and merged into three staged interacting networks, representing the Pre, TvN, and Meta progressive states of HNSCC.For reasons of the inherent noise in the HNSCC transcriptome, we developed a strategy to capture the essential themes by focusing on the enriched signaling pathways as well as the topological properties of the interacting networks. In the verified gene lists, findings were more stably shown in HNSCC but the scope might be too limited. In contrast, using the full gene lists might facilitate findings of significant modules, which might be obscure when data were scarce. Therefore, the bounded fold changes of the full gene lists and the verified gene lists of Pre, TvN and Meta interacting networks, respectively. The density (average degree) of the networks was similar for each stage, and all of them contained a major component (a connected subset) of the size around 2000 genes. We did network topological analyses and identified significant inter-modular hubs with the highest informational scores. Likewise, intra-modular hubs of the highest connectivity for each stage of comparison were also listed in Top 10 enriched canonical pathways resulted from the IPA analysis using the verified gene lists were quite different from those using the full gene lists. The −log of the canonical pathways analyzed with the verified genes list were more significant than those with the full gene lists. Meta was noted, particularly HLA-G in MHC I and HLA-DRB1 in MHC II. CALR, the endoplasmic reticulum-residing chaperone, calreticulin, was found differentially expressed in Pre and Meta; and presented itself as the hub connecting MHC I, the complement system, and THBS1.We sought to explore the global HNSCC transcriptome by looking into the enriched antigen presentation and integrin signaling pathways . EmergenACTN2, CAPN3 and TTN in Pre and TvN; and ILK, RHO-G and VCL in Meta. GRB2, ITGA5, ITGB6, ITGB7 and MAPK8 were distinguished as topologically significant hubs in the TvN interacting networks. Network-based approach to address the complex mechanisms underlying the integrin adhesome has been sought out by researchers ITGA3, ITGA5, and the RhoGTPases were required in the force-mediated matrix remodeling, by which the leading stromal fibroblasts were able to generate tracks to support SCC invasion. To exploit the biological significance of the interacting networks in the enriched pathways, we compared the topological informational scores of the integrin family with the percentage of matrix contraction due to knockdown of integrins by siRNA in stromal fibroblasts . The informational scores derived from the topology of interacting networks were developed to estimate the perturbed pathological effects, i.e. blocked signaling information. Not all of the integrins were differentially expressed across three stages; hence, we could not correlate the estimated pathological effects beyond the TvN networks. Nonetheless, based on the strong association between the estimated biological significance and the experimental findings, we are convinced that network-based meta-analyses of the evolving HNSCC transcriptome could indeed recapitulate the underlying nature of disease progression.Gaggioli and colleagues roblasts . With reS100As, CD48, and ECM1, as well as 6p21, 19p13 and 19q13 were highlighted. It was of interest to know if genes co-localized in a hot-spot would interact with those within another hot-spot. In the antigen presentation pathway, MHC complex, TAP1 and TNF were located in 6p21, whereas another interacting gene, CALR, was in the other hot-spot of 19p13. We compared hot-spots of differential gene activities to those of genomic alterations reported by Weber and colleagues HIST1H4s were found repressed in Pre and TvN; HIST1H2s induced in TvN; and HIST1H3s repressed in TvN.In In order to fully utilize the powerful gene expression profiling, challenges remained in data integration and in gaining meaningful insights. The purpose of this meta-analysis aimed at investigating the transcriptional profiles of HNSCC via a systems-level and knowledge-based network approach by means of synthesizing previous research efforts. We showed that gene-gene interplays in the interacting networks, which were quantitatively analyzed with topological informational scores and qualitatively visualized with bounded fold changes, illuminated the underlying biological events in three progressive stages of HNSCC. To date, we conducted for the first time a genome-wide meta-analysis in the context of knowledge-based networks and systematic reviews. We took the first step to unravel the pathophysiology of HNSCC via a systems-biology approach. Moreover, we provided a platform for the HNSCC research community to make strides in advancing our knowledge and future progress.CALR, TAP1, HLA-DQB2, PTEN, HRAS, RHOA, ITGA3 and IT GA5 from the topological scorings and the differential gene activities in the evolving HNSCC transcriptome. Remarkably, the estimated informational scores derived from the integrin signaling networks not only supported previous findings of Gaggioli et al. in vivo. Most of the differentially expressed genes in the antigen presentation and integrin signaling pathways fell into hot-spot regions of 6p21 and 17q21. Moreover, several highlighted hot-spots of differential gene activities, such as 19p13 and 19q13, co-localized to previous implicated regions of genomic alterations by Weber et al. We demonstrated that the perturbation of genes in the interacting networks could be estimated by the topological properties. In the enriched antigen presentation and integrin signaling pathways, we recognized significant roles of It is of importance to acknowledge that the approach taken in this meta-analysis, including converting identifiers, standardizing bounded fold changes, and analyzing the topology of knowledge-based networks, are innovative but primitive. Therefore, further experimental efforts to consolidate the demonstrated findings are crucial. Nonetheless, applying a standard template for each study, so that the subsequent meta-analyses could be feasible, was indeed painstaking. Currently, we do not have a standard guideline to report genome-wide experiments in functional context. As ‘gene’ has become a vague definition and new ‘genon’ concept been proposed Table S1Included studies of microarray based differential gene expression profiles of HNSCC.(0.18 MB PDF)Click here for additional data file.Table S2Topologically significant genes in enriched canonical pathways.(0.06 MB PDF)Click here for additional data file.Table S3Most frequently reported genes in 6p21, 19p13, and 19q13.(0.09 MB PDF)Click here for additional data file.Text S1Details of the PubMed Query, compiled format for each study, and details of the anatomical-site-specific genes in TvN.(0.11 MB PDF)Click here for additional data file.Figure S1Detailed Figure of the Integrin Signaling Networks in Pre.(0.26 MB PDF)Click here for additional data file.Figure S2Detailed Figure of the Integrin Signaling Networks in TvN.(0.38 MB PDF)Click here for additional data file.Figure S3Detailed Figure of the Integrin Signaling Networks in Meta.(0.24 MB PDF)Click here for additional data file.Figure S4Detailed Figure of the Merged Integrin Signaling Networks, with node coloring of the differential gene expression profiles of the Meta stage.(0.56 MB PDF)Click here for additional data file.Figure S5Detailed Figure of the Merge Networks of the Antigen Presentation Pathway, with node coloring of the differential gene expression profiles of the Meta stage.(0.16 MB PDF)Click here for additional data file.


APC mutations. The relationships between the spectrum of mutations and extracolonic manifestations are quite well known, but they need to be further defined.Familial adenomatous polyposis (FAP) is an autosomal dominant hereditary disease characterized by multiple colorectal adenomatous polyps and frequent extracolonic manifestations. An attenuated form of FAP (AFAP) is diagnosed based on a milder colorectal phenotype, and the colorectal phenotype of (A)FAP has been linked to germline APC mutations, but no large deletions, were identified in the APC locus of 8 (A)FAP patients, and 5 of the mutations, c.446A > T , c.448A > T (p.Lys150X), c.454_457insAGAA (p.Glu152ArgfsX17), c.497insA (p.Thr166AsnfsX2), and c.1958G > C (p.Arg653Ser), were novel mutations. In one patient the p.Asp149Val mutation and p.Lys150X mutation were detected in the same APC allele. The c.1958G > C mutation was located in the last nucleotide of exon 14, and RT-PCR analysis revealed that the mutation resulted in abnormal splicing. The above findings meant that a nonsense mutation, a frameshift mutation, or an exonic mutation leading to abnormal splicing was found in every patient. The following phenotypes, especially extracolonic manifestations, were observed in our (A)FAP patients: (1) multiple gastroduodenal adenomas and early-onset gastric carcinoma in AFAP patients with an exon 4 mutation; (2) a desmoid tumor in two FAP patients with a germline APC mutation outside the region between codons 1403 and 1578, which was previously reported to be associated with the development of desmoid tumors in FAP patients; (3) multiple myeloma in an AFAP patient with an exon 4 mutation.Nine germline APC mutations, 5 of them were novel, were identified in 8 Japanese (A)FAP patients, and some associations between germline APC mutations and extracolonic manifestations were demonstrated. These findings should contribute to establishing relationships between germline APC mutations and the extracolonic manifestations of (A)FAP patients in the future.Nine germline  MutYH gene [adenomatous polyposis coli (APC), which encodes a 2843-amino-acid protein that contains a variety of functional domains involved in cell cycle control, differentiation, transcription, migration, and apoptosis [APC gene, and the lifetime penetrance of the disease is close to 100% [APC mutations in AFAP patients have been found to occur at the 5' end and 3' end and in a specific region of exon 9 of the APC gene, in contrast to the germline APC mutations in classical FAP patients, which are found in other locations [APC mutations in patients with multiple colorectal polyps is very important to the proper management of (A)FAP.Familial adenomatous polyposis (FAP) is an autosomal dominant familial cancer syndrome characterized by the early onset of large numbers of adenomatous polyps throughout the entire colon and a nearly 100% lifetime risk of colorectal cancer (CRC) if the colon is not removed [tYH gene . However to 100% . Some FA to 100% -8. The gAPC mutations between codons 457 and 1444, and desmoid tumors develop only in patients having mutations between codons 1403 and 1578 [APC genotypes and FAP phenotypes are well known, they need to be further defined. In this study we investigated the genes of 8 Japanese (A)FAP patients for germline APC mutations, and we identified 9 germline APC mutations, including 5 novel ones. We also discuss possible relationships between the germline APC mutations and extracolonic manifestations in our (A)FAP patients.A number of extracolonic phenotypic manifestations are associated with FAP: upper gastrointestinal tract polyps and cancer, desmoid tumors, thyroid cancer, hepatoblastoma, congenital hypertrophy of the retinal pigment epithelium (CHRPE), and other extracolonic malignancies ,3. One oBlood samples were obtained from 5 patients with classical FAP and 3 patients with attenuated FAP, all of whom appeared to be unrelated, in the hospital of Hamamatsu University School of Medicine. Written informed consent was obtained from every patient. Lymphocyte genomic DNAs were extracted from the blood samples with a QIAamp DNA Blood Maxi kit . This study was approved by the Institutional Review Board of the Hamamatsu University School of Medicine (18-4).APC and their boundary regions were amplified by polymerase chain reaction (PCR) and directly sequenced with ABI BigDye Terminator Ready Reaction Mix  and an ABI 3100 Genetic Analyzer (Applied Biosystems) [The 1st-15th exons of systems) . InformaThe splicing efficiency of the wild-type allele and the mutant-type allele of the patient with c.1958G > C mutation was predicted by using the Berkeley Drosophila Genome Project (BDGP) splice prediction program . The effRNAs were extracted from blood samples with a PAXgene Blood RNA Kit (QIAGEN) and converted to first-strand cDNAs by using a SuperScript First-Strand Synthesis System for reverse transcription (RT)-PCR  according to the supplier's protocol . RT-PCR A MLPA kit (P043 APC) was purchased from MRC-Holland , and reactions were carried out according to the manufacturer's instructions. Probe ratios below 0.7 and above 1.3 are regarded as indicative of a decrease and increase, respectively, of gene dosage.APC coding regions and exon-intron boundaries enabled identification of a total of 9 germline APC mutations in 8 unrelated Japanese (A)FAP patients , c.448A > T (p.Lys150X), c.454_457insAGAA (p.Glu152ArgfsX17), c.497insA (p.Thr166AsnfsX2), and c.1958G > C (p.Arg653Ser), had never been reported in any articles according to the information in the Human Gene Mutation Database or in the APC variant databases in the Leiden Open Variation Database (LOVD) [APC fragments revealed that the c.446A > T mutation and c.448A > T mutation detected in Patient 1 were located on the same APC allele  , and none Figure . Since te Figure . The c.1e Figure . The remeviously .APC mutations, i.e., c.1956C > T, c.1957A > C, and c.1957A > G very close to c.1958G > C, have previously been reported to induce abnormal splicing of exon 14 [The novel mutation c.1958G > C detected in Patient 4 was localized in the last nucleotide of exon 14, and three germline  exon 14 . Moreove exon 14 . CalculaAPC exon 4 of the DNA derived from Patient 2  in Patient 2. Thus, it is likely that the overlapping caused the disruption of the MLPA reactions in the DNA. The other decreased signal was detected with the p.1309 mutation-specific probe in Patient 8 FAP patients.To better evaluate the state of the genomic DNA of (A)FAP patients, MLPA analysis, which is useful for detecting large deletions and duplications, was also performed on all 8 samples. No increased signals were detected, but decreased signals were detected in two patients. One decreased signal was detected in 2 Figure . However8 Figure . These rAPC exon 4 had been diagnosed with AFAP because of their attenuated colorectal phenotypes. From 40 to 100 colorectal polyps were detected in Patient 1. Patient 2 was found to have a relatively small number of colorectal polyps at 29 years of age, and clinical follow up was performed instead of surgical treatment. At 51 years of age, however, an early-stage CRC and approximately 100 colorectal adenomatous polyps were detected, and total colectomy was performed. A sister of Patient 2 was also diagnosed with AFAP and found to have the same APC mutation, but none of the 6 unaffected members of this family was found to have the family-specific mutation. Colon fiberscopy was performed for the first time in Patient 3 when he was 69 years old because of rectal bleeding, and more than 100 colorectal adenomatous polyps and multiple advanced-stage CRCs were observed. Total colectomy was performed, but the patient died of liver and lung metastases 7 years later. By contrast, more than 300 colorectal adenomatous polyps were found in each of the other 5 patients, who were diagnosed with classical FAP. The mother of Patient 4 and the daughter of Patient 5 were found to have their family-specific APC mutation, consistent with their FAP phenotype. Among the extracolonic manifestations, gastroduodenal polyps, which are also common in FAP patients, were observed in all of the patients with classical and attenuated FAP in this study. Most of the polyps in the stomach were histologically diagnosed as fundic gland polyps. However, multiple adenomas were observed in the stomach and duodenum of Patients 1, 3, 4, 5, and 7. Desmoid tumors are common in FAP patients and were observed in Patients 5 and 7. Malignant neoplasms in the form of gastric carcinoma, multiple myeloma, duodenal carcinoma, small intestinal carcinoma, and thyroid carcinoma developed in Patient 1, Patient 3, Patient 4, Patient 5, and Patient 8, respectively. No extracolonic manifestations were detected in the other (A)FAP affected members of any of the families, or such information was unavailable.The clinical phenotypes of all 8 patients are summarized in Table APC genes of 8 Japanese (A)FAP patients from 8 unrelated families revealed a nonsense mutation, a frameshift mutation, or an exonic mutation leading to abnormal splicing, all of which resulted in the production of a truncated APC protein, in every patient. No large deletions or duplications in the APC locus were detected in any of the patients. Five of the 9 germline APC mutations detected in this study had never been reported before, meaning that they are novel mutations. Since two mutations, c.446A > T  and c.448A > T (p.Lys150X), are on the same allele and located close to each other, it is possible that these two mutations are in complete linkage disequilibrium but are not two independent mutations. Consistent with the previous finding that mutations in the 5' and 3' ends and in exon 9 of the APC gene are associated with having the attenuated type of FAP [Sequencing analysis, RT-PCR analysis, and MLPA analysis of the e of FAP , the mutAPC mutations and extracolonic manifestations are still not fully understood. Furthermore, as the number of patients diagnosed with (A)FAP has increased, a broad range of variable extracolonic manifestations has gradually come to be recognized in (A)FAP patients. Based on the results of APC mutations and extracolonic manifestations observed in our study, we focused our attention on the following three issues. First, fundic gland polyps, not gastric adenoma, have been reported to be the main gastric lesions in AFAP patients [APC exon 4, and a gastric adenocarcinoma was also found in one of them at 34 years of age. As far as we know [APC mutation in the gastric carcinogenesis remains largely unknown. There have been reports of gastric adenocarcinomas in (A)FAP patients having arisen from a fundic gland polyp or adenoma, and the reports suggested the existence of an adenoma-adenocarcinoma sequence in their carcinogenesis [APC inactivation status in the adenomas and adenocarcinomas detected in our patients may help to better understand the mechanism of the involvement of APC mutations in tumorigenesis. In addition to genetic factors, various environmental factors have been reported to affect the risk of gastric cancer [APC mutation between codons 1403 and 1578 in FAP patients and the occurrence of desmoid tumors [APC mutation outside the region, i.e., in codon 664 and codon 1249. Some other recent papers have also reported the occurrence of desmoid tumors in FAP patients with APC mutations outside the region between codons 1403 and 1578 [APC mutations between codons 1403 and 1578, some of them occur outside the region. The third issue that we focused our attention on is that a multiple myeloma was detected in one of our 3 AFAP patients with a germline exon 4 mutation. This is the first report of complication of AFAP by multiple myeloma. However, evidence of APC involvement, such as a second somatic mutation of APC in multiple myeloma, needs to be found in order to rule out the possibility that the occurrence of the multiple myeloma was a coincidental unrelated event. We think that although the number of cases analyzed was relatively small, the above three findings will contribute to establishing relationships between germline APC abnormalities and clinical phenotypes in (A)FAP patients and to better characterizing the differences between APC-related polyposis and MutYH-associated polyposis in the future. However, since many examples of deviations from observed APC genotype-FAP phenotype correlations and highly variable phenotypic traits have been reported [APC genotype may be involved in producing the (A)FAP phenotype.Knowledge of genotype-phenotype correlations in (A)FAP has been accumulating, and it is useful in the clinical management of (A)FAP families, but the relationships between the locations of the patients ,8. Inter we know ,8, this  we know -26, but ogenesis -25. Howec cancer -29, enviand 1578 ,31. Thusreported ,32-34, iAlthough a nearly 100% risk of CRC has been reported in patients with classical FAP, the lifetime risk of CRC in AFAP patients is unclear. At the time this study was performed CRC had been diagnosed in Patient 2 at 51 years of age and Patient 3 at 69 years of age, but not in Patient 1, who was 38 years old. Lifetime risk of CRC is an important factor in the clinical management and genetic counselling of AFAP patients, especially because it affects the decision as to whether to proceed with prophylactic colectomy. The results of this study should contribute to determining the lifetime risk of CRC in AFAP patients in the future.APC gene, causes abnormal splicing. Since APC mRNA transcript analyses in previous studies have demonstrated that exonic single-base substitutions of c.423G > T, c.834G > C, c.1869G > T, c.1918C > G, c.1956C > T, c.1957A > C, and c.1957A > G affect splicing [APC exonic mutation that has been demonstrated to result in abnormal splicing. Interestingly, most (6 out of 8) of the exonic mutations associated with abnormal splicing have been located in exon 14, but the reason for this clustering is unclear.The results of the RT-PCR analysis in this study showed that a G to C transversion at c.1958, which corresponds to the last nucleotide of exon 14 of the splicing ,35-37, cAPC mutations, 5 of which were novel, were identified in 8 Japanese (A)FAP patients. The following three findings regarding the relation between the location of the germline APC mutations and extracolonic manifestations were also obtained in this study: 1) severe gastric lesions occurred in AFAP patients with an exon 4 mutation, 2) desmoid tumors developed in FAP patients with germline APC mutations outside the region between codons 1403 and 1578, 3) a multiple myeloma developed in an AFAP patient with an exon 4 mutation. These findings should contribute to increasing our knowledge of the associations between APC genotypes and (A)FAP phenotypes, which are informative for proper clinical management and genetic counselling of (A)FAP patients and their families.In the present study, 9 germline The authors declare that they have no competing interests.HT carried out the mutation detection and molecular genetic analyses, collected up the clinical data, participated in the design of the study, and drafted the manuscript. KS participated in the design of the study and drafted the manuscript. HY extracted the total RNAs from blood samples. MM, SO, YT, KO, TT, HM and TN identified relevant patients for genetic testing and were responsible for clinicopathological data. HS and MM conceived of the study, participated in the design of the study, and drafted the manuscript. All authors read and approved the final manuscript.


A rise in obesity, poor-quality diets, and low physical activity has led to a dramatic increase in the number of Americans with metabolic syndrome and diabetes. Our objective was to determine the effect of a short-term, multifaceted wellness program carried out in a church setting on weight, metabolic syndrome, and self-reported wellness.Forty-one overweight or obese adults in a church congregation provided fasting blood samples and answered a wellness questionnaire before and after completing an 8-week diet and exercise program. We also measured weight, body fat, body mass index, and waist and hip circumference.The intervention decreased weight, body fat, and central adiposity; improved indexes of metabolic syndrome; and increased self-reported wellness.A multifaceted wellness intervention that emphasizes diet and exercise can rapidly influence weight, insulin resistance, metabolic syndrome, and self-reported wellness. During the past 4 decades, the prevalence of obesity in the United States has increased dramatically. If these trends continue, 83% of adults will be overweight or obese by 2030 . ObesityNutrition and physical activity are key lifestyle factors that affect the incidence of obesity, metabolic syndrome, and other diseases. Even modest weight loss improves dyslipidemia, insulin resistance, and estimated 10-year cardiovascular disease risk -7. MilliBecause wellness programs can reduce the cost of health care and generate a substantial return on investment  . Pregnant women were excluded because the program involved caloric restriction and moderate to vigorous exercise. Pregnancy was the only exclusion criterion; all other congregants who received permission from their primary care physician and provided written informed consent were allowed to participate. This study was conducted according to approved human studies guidelines and was approved by the institutional review board of Wake Forest University Health Sciences.2) and 46 of whom were overweight or obese (BMI ≥25 kg/m2). Healthy-weight participants did not restrict calories and were excluded from analysis; of the overweight or obese participants, 5 did not participate in the entire intervention and were also excluded from analysis.A total of 59 participants began the program, 13 of whom were healthy weight  that described the dietary and exercise recommendations of the program. Participants also attended 2 weekly educational programs  in which the scientific rationale behind the recommendations was explained. The dietary recommendations had 5 components:Calorie reduction. Overweight and obese participants were told to reduce calorie intake by 20% from their individual baseline as determined by a predictive equation for resting energy expenditure  for the Increased fiber intake. A daily fiber intake of 16 g per 1,000 kcal consumed and a 70:30 insoluble-to-soluble fiber ratio was recommended.trans-resveratrol, anthocyanins, and ellagic acids and green teas high in catechins were recommended. In the final 4 weeks, participants were allowed red wine (4-6 glasses/wk) and dark chocolate (43-99 g/d).Increased polyphenol intake. Fruits and vegetables high in Increased intake of long-chain omega-3 fatty acids. Fatty fish and fish oil supplements were recommended .Increased intake of short-chain omega-6 fatty acids. Borage oil supplements were recommended . These doses and ratios of omega-3 and omega-6 fatty acids were previously determined in our laboratory .Participants were provided with heart rate monitors and were encouraged to exercise at least 30 minutes per day at an appropriate level (50%-75% of maximum heart rate for age during weeks 1-3 and 70%-85% of maximum heart rate for age thereafter). Participants were told to dedicate 3 days per week to aerobic exercise and 2 days for circuit training, which consisted of aerobic warm-up and cool-down combined with weight training designed to work 8 to 10 muscle groups. The intensity of the recommended exercise increased from mostly light at the beginning of the intervention to mostly vigorous by the end. Instructions for specific aerobic workouts and circuit training were described in the program handout. Participants received instruction in performing each exercise at a level appropriate to his or her fitness level during the first weekly exercise session at the church. They were encouraged to purchase resistance bands and hand weights for use in their exercise routines. Exercise was undertaken independently and once weekly at the church.Participants met weekly for body measurements, group exercise sessions at the church, dietary counseling, and group support. This church group took a faith-based approach to mutual support, encouragement, prayer, and striving to make their bodies healthy. Participants kept logs of their food intake and exercise to facilitate lifestyle changes and accountability.At the beginning of the intervention, we collected baseline urine, fasting blood samples, anthropomorphic measurements , blood pressure, and resting heart rate. Thereafter, body fat and BMI were measured at weeks 1, 4, and 8. At the end of the 8-week intervention, all fasting samples and measurements were obtained again. Follow-up anthropomorphic measurements were obtained 5 and 10 weeks after the intervention. In addition to anthropomorphic measurements, 6 surrogate markers of insulin resistance and diabetes — fasting insulin, fasting glucose, homeostatic model assessment of insulin resistance (HOMA) , hemogloThroughout the study, the same person performed waist and hip measurements. Weight, body fat, and BMI were measured by using a Tanita BF-350 body fat scale . The North Carolina Baptist Hospital Clinical Laboratories  measured complete blood counts and differentials. Serum was separated, aliquoted, and frozen until used to measure levels of lipid, glucose, and other metabolites according to standard clinical laboratory methods or previously published methods .At baseline and week 8, participants completed a wellness questionnaire, a modified self-rated health and wellness survey  designedt tests to assess changes in continuous variables. We used analysis of variance to determine whether the changes differed by sex. We used an exact McNemar test to assess changes in dichotomous variables . All analyses were conducted by using SAS version 9.1 . We considered P values less than .05 to be significant.We used paired Of 46 overweight or obese participants who began the program, 41 (27 women and 14 men) completed it. Participants' mean age was 53 years , and all participants were white with the exception of 1 female African American participant. At baseline, all participants exceeded the healthy cutoff value for percentage of body fat (≤31% for women and ≤21% for men); 17 women and 13 men also exceeded the healthy cutoff value for waist-to-hip ratio (≤0.8 for women and ≤0.9 for men). Eighteen participants completed a medical history, and of these, 12 reported immunologic conditions , 8 reported cardiovascular disease (such as high blood pressure or history of heart attack), 5 reported high cholesterol, and 2 reported diabetes.During the 8-week intervention, men lost an average of 5.9 kg (13.1 lb) and women lost an average of 4.8 kg (10.5 lb), which is approximately a 6% decrease in body weight for both men and women . After tSimilarly, body fat and BMI decreased in both men and women during the 8 weeks of the program. In women, these trends continued during the 10-week follow-up. In men, body fat remained stable during the follow-up period, but BMI began to increase after 5 weeks . Waist cTwenty-seven participants  turned in complete wellness questionnaires at both baseline and 8 weeks. Participants reported significant improvements in most domains .P = .02) and men . At baseline, 18 of 41 participants were classified as having metabolic syndrome (10 women and 8 men). After the intervention, that number had decreased to 10 (6 women and 4 men) (P < .001).After the intervention, waist circumference, a measure of central adiposity, was significantly decreased in women and men, and systolic blood pressure was significantly decreased in men . Most otAlthough fasting glucose levels did not change , all othThis multifaceted intervention significantly improved the conditions that define metabolic syndrome and reduced the number of participants who had metabolic syndrome. We also found improvements in several measures of insulin resistance. These observations suggest that a multifaceted approach to wellness that incorporates nutrition education and exercise in a supportive, faith-based environment can promote healthy lifestyle changes in overweight and obese adults.Our findings contrast with results of several commercial weight loss programs, which have high attrition rates, rapid weight regain, and poor adherence . More thSignificant changes in indexes of metabolic syndrome and insulin resistance were achieved in a short time and in participants who lost only 6% to 8% of their original body weight and 9% to 13% of their original fat mass. This finding suggests that decreased fat mass is not the only factor responsible for the decreased insulin resistance. Whether the changes in metabolic syndrome were associated with those in insulin resistance is not clear. A recent study showed that metabolic syndrome is a significant predictor of diabetes, increasing the risk by a factor of 3.5 to 5.2 ; this asOur intervention incorporated several dietary and exercise strategies. Consequently, determining the precise mechanisms responsible for the improvements is difficult. Several studies have found that exercise independently decreases glucose levels and risk of type 2 diabetes ,20, and The specific dietary recommendations in this study likely contributed to the observed improvements. A high-fiber diet, as recommended in this study, improves glycemic control ,23, and This study has several limitations. First, the program was conducted at only 1 church, so the results cannot be generalized and the program may not be feasible in other settings. The efficacy of the program should be evaluated in groups that differ in age and ethnic and racial composition. Second, because of the multifaceted nature of the intervention, we cannot elucidate specific aspects that affected insulin resistance or metabolic syndrome. Third, physical and emotional wellness were assessed by self-report; however, self-perception of wellness is a complex sum of individual health values and social and environmental influences , all of In conclusion, we found that a multifaceted, church-based wellness program that emphasizes education, a healthy diet, weight loss, physical activity, weekly coaching, and accountability can rapidly (within 8 weeks) decrease insulin resistance and risk of metabolic syndrome.