New product, old problem(s): multistate outbreak of Salmonella Paratyphi B variant L(+) tartrate(+) infections linked to raw sprouted nut butters, October 2015.

A cluster of Salmonella Paratyphi B variant L(+) tartrate(+) infections with indistinguishable pulsed-field gel electrophoresis patterns was detected in October 2015. Interviews initially identified nut butters, kale, kombucha, chia seeds and nutrition bars as common exposures. Epidemiologic, environmental and traceback investigations were conducted. Thirteen ill people infected with the outbreak strain were identified in 10 states with illness onset during 18 July-22 November 2015. Eight of 10 (80%) ill people reported eating Brand A raw sprouted nut butters. Brand A conducted a voluntary recall. Raw sprouted nut butters are a novel outbreak vehicle, though contaminated raw nuts, nut butters and sprouted seeds have all caused outbreaks previously. Firms producing raw sprouted products, including nut butters, should consider a kill step to reduce the risk of contamination. People at greater risk for foodborne illness may wish to consider avoiding raw products containing raw sprouted ingredients.

Notes from the Field: Clostridium perfringens Gastroenteritis Outbreak Associated with a Catered Lunch - North Carolina, November 2015.

During November 2015, the North Carolina Division of Public Health was notified by the Pitt County Health Department (PCHD) that approximately 40 persons who attended a catered company Thanksgiving lunch the previous day were ill with diarrhea and abdominal pain. The North Carolina Division of Public Health and PCHD worked together to investigate the source of illness and implement control measures. Within hours of notification, investigators developed and distributed an online survey to all lunch attendees regarding symptoms and foods consumed and initiated a cohort study. A case of illness was defined as abdominal pain or diarrhea in a lunch attendee with illness onset <24 hours after the event. Risk ratios (RRs) and 95% confidence intervals (CIs) were estimated for all menu items. Among 80 attendees, 58 (73%) completed the survey, including 44 respondents (76%) who reported illnesses meeting the case definition; among these, 41 (93%) reported diarrhea, and 40 (91%) reported abdominal pain. There were no hospitalizations. Symptom onset began a median of 13 hours after lunch (range = 1-22 hours). Risk for illness among persons who ate turkey or stuffing (38 of 44; 86%), which were plated and served together, was significantly higher than risk for illness among those who did not eat turkey or stuffing (six of 14; 43%) (RR = 2.02; 95% CI = 1.09-3.73).

Hippocampal dysgenesis and variable neuropsychiatric phenotypes in patients with Bardet-Biedl syndrome underline complex CNS impact of primary cilia.

The Bardet-Biedl syndrome (BBS) is a rare ciliopathy clinically defined by the association of retinitis pigmentosa, polydactyly, obesity, kidney disease and cognitive impairment. The cognitive functioning, behavioral phenotype, prevalence of psychiatric diseases and memory performances of a cohort of 34 patients with BBS were evaluated and a systemic brain magnetic resonance imaging (MRI) was performed. The patients' cognitive functioning was of marked variable efficiency ranging from normal to disabling performances. Neuropsychological disorders such as slow thought process, attention difficulties and obsessive-compulsive traits were observed. Our main finding was hippocampal dysgenesis, diagnosed by MRI, found in 42.31% of the patients in this cohort. Moreover, we show that BBS proteins are expressed in the human hippocampus and in the human brain in the normal subject. Recent literature in the murine model shows that hippocampal neurogenesis, in particular in the adult mouse, requires an intact primary cilia. These results encourage us to further investigate the possible role of BBS proteins in the hippocampus and related central nervous system structures.

The Renpenning syndrome spectrum: new clinical insights supported by 13 new PQBP1-mutated males.

Since the first reports of polyglutamine-binding protein 1 (PQBP1) mutations in Renpenning syndrome and related disorders, the spectrum of PQBP1-linked clinical manifestations has been outlined from rare published case reports. The phenotypic description is often obtained from medical archives, and therefore, heterogeneous. Moreover, some aspects such as brain imaging or cognitive and behavioral functioning are rarely described. In this study, 13 PQBP1-mutated French patients were subjected to a standardized clinical, cognitive and behavioral assessment. Physical measurements of their relatives were also collected. We report on a recognizable clinical and radiological phenotype. All patients presented with microcephaly, leanness and mild short stature, relative to familial measurements. Three new clinical features are described: upper back progressive muscular atrophy, metacarpophalangeal ankylosis of the thumb and velar dysfunction. The specific facial dysmorphic features included at least four of the following signs: long triangular face, large ridged nose, half-depilated eyebrows, dysplastic or protruding ears and rough slightly sparse hair. An over-aged appearance was noticed in elderly patients. Cortical gyrification was normal based on available magnetic brain imaging of six patients. PQBP1-linked microcephaly (or Renpenning syndrome) is an X-linked mental retardation syndrome, which has clinically recognizable features.

Identification of 28 novel mutations in the Bardet-Biedl syndrome genes: the burden of private mutations in an extensively heterogeneous disease.

Bardet-Biedl syndrome (BBS), an emblematic disease in the rapidly evolving field of ciliopathies, is characterized by pleiotropic clinical features and extensive genetic heterogeneity. To date, 14 BBS genes have been identified, 3 of which have been found mutated only in a single BBS family each (BBS11/TRIM32, BBS13/MKS1 and BBS14/MKS4/NPHP6). Previous reports of systematic mutation detection in large cohorts of BBS families (n > 90) have dealt only with a single gene, or at most small subsets of the known BBS genes. Here we report extensive analysis of a cohort of 174 BBS families for 12/14 genes, leading to the identification of 28 novel mutations. Two pathogenic mutations in a single gene have been found in 117 families, and a single heterozygous mutation in 17 families (of which 8 involve the BBS1 recurrent mutation, M390R). We confirm that BBS1 and BBS10 are the most frequently mutated genes, followed by BBS12. No mutations have been found in BBS11/TRIM32, the identification of which as a BBS gene only relies on a single missense mutation in a single consanguineous family. While a third variant allele has been observed in a few families, they are in most cases missenses of uncertain pathogenicity, contrasting with the type of mutations observed as two alleles in a single gene. We discuss the various strategies for diagnostic mutation detection, including homozygosity mapping and targeted arrays for the detection of previously reported mutations.

Confirmation of TFAP2A gene involvement in branchio-oculo-facial syndrome (BOFS) and report of temporal bone anomalies.

Branchio-oculo-facial syndrome (BOFS) is an autosomal-dominant condition characterized by three main features, respectively: branchial defects, ocular anomalies, and craniofacial defects including cleft lip and/or palate (CL/P). We report on one family with three affected, and two sporadic cases that have been found to carry missense mutations in the newly reported BOFS gene: TFAP2A. This report confirms the involvement of this transcription factor in this developmental syndrome with clinical variability. Moreover, we present CT scan temporal bone anomalies in the familial cases, related to branchial arch defects, highlighting the importance of radiological investigations for differential diagnosis.

[Cholinergic hypothesis in psychosis following traumatic brain injury and cholinergic hypothesis in schizophrenia: a link?]. / Théorie cholinergique dans les psychoses après un traumatisme crânien et dans la schizophrénie: un lien?

INTRODUCTION: While traumatic brain injury is a major public health issue, schizophrenia-like psychosis following traumatic brain injury is relatively rare and poorly studied. Yet the risk of developing schizophrenia-like psychosis after traumatic brain injury is 3 times more important than in the general population. LITERATURE FINDINGS: Risk factors associated with onset of psychosis after traumatic brain injury include: left hemispheric lesions, closed head injury and coma of duration superior to 24 hours. Most patients develop symptoms of psychosis after a moderate to severe traumatic brain injury and often have lesions of the frontal and temporal lobes. CHOLINERGIC HYPOTHESIS: ARGUMENTS: Neuropathologic, electrophysiological and pharmacologic evidence show that cognitive impairment including attention, memory and executive functioning impairment may be related with cholinergic dysfunction in patients with traumatic brain injury. The cholinergic hypothesis is also incriminated in the genesis of schizophrenia. The same biochemical disorders found in schizophrenia which imply many neurotransmitters are often present immediately after traumatic brain injury. However in chronic cognitive disorders secondary to traumatic brain injury, the cholinergic system alone seems to be specifically implied. This is due to the fragility of the cholinergic fibres and a chronic yet reversible reduction of the cholinergic reserves after traumatic brain injury. Cholinergic function can be studied by the P50 evoked response to paired auditory stimuli.While this is disturbed in patients presenting with cognitive impairment after traumatic brain injury its normalisation can be obtained after administration of an acetylcholine esterase inhibitor. In schizophrenic patients there is also an abnormal P50 evoked response due in part to a low number of alpha 7 nicotinic receptors which are implicated in sensory filtering in the frontal lobe. Moreover in schizophrenia, post-mortem studies show a negative correlation between the activity of acetylcholine transferase in the parietal cortex and the severity of the cognitive deficits, as well as a lesser density of the muscarinic M1 and M4 receptors in the frontal lobe. The lower concentration of M1 receptors in the frontal cortex is correlated with the severity of the positive symptoms. THERAPEUTICAL PERSPECTIVES: Antipsychotics have emerged as the first line treatment of psychotic disorders. In research, their ability for enhancing cognitive function could result in the increase of acetylcholine in the medial prefrontal cortex. Acetylcholinesterase inhibitors have been widely used for treatment of cognitive impairment in Alzheimer's disease. Galantamine could be interesting in schizophrenia and psychosis following traumatic brain injury because it has a dual mechanism of action: selective competitive inhibition of acetylcholinesterase and allosteric potentialisation of nicotinic receptor response. Therefore Galantamine remains active in nicotine addicted schizophrenic patients who may smoke as an auto treatment. Galantamine has shown efficacy in adjunction to Risperidone in one patient presenting with psychosis following traumatic brain injury and in 3 case reports of schizophrenic patients. CONCLUSION: Further systematic studies are needed to confirm this hypothesis.

Demonstration that ethanol inhibits bone matrix synthesis and mineralization in the rat.

The effects of ethanol on bone and mineral metabolism were investigated in 3 groups of male rats. The first group received ethanol administered as 36% of caloric content in a liquid diet for 3 weeks. A second group of pair-fed animals was given the same liquid diet, except that sucrose was substituted isocalorically for ethanol. A third group of rats was fed standard laboratory chow. The ethanol-treated rats gained significantly less weight than laboratory chow-fed controls but gained the same weight as the pair-fed animals. Ethanol-treated rats had a modest but significant decrease in mean serum calcium compared to pair-fed controls (10.3 +/- 0.1 vs. 10.6 +/- 0.1 mg/dl, p less than .001). Mean serum phosphate, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and immunoreactive parathyroid hormone were the same in the 3 groups. The ethanol-treated animals showed significant decreases in mean tibial length (1.88 +/- 0.01 vs. 1.98 +/- 0.02 cm, p less than .01), mean endosteal bone formation rate (0.0006 +/- 0.0001 vs. 0.0026 +/- 0.0003 mm3/day, p less than .001) and mean periosteal bone formation rate (0.022 +/- 0.001 vs. 0.026 +/- 0.001 mm3/day, p less than .01) compared to the pair-fed controls. The ethanol-treated rats demonstrated significant decreases in mean periosteal mineralization rate (7.5 +/- 0.3 vs. 10.3 +/- 0.6 micron/day, p less than .01) and mean periosteal apposition rate (8.5 +/- 0.5 vs. 11.0 +/- 0.8 micron/day, p less than .05) and a significant increase in mean periosteal osteoid thickness (15.5 +/- 1.4 vs. 10.4 +/- 0.8 micron, p less than .01) compared to pair-fed controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Prostaglandin E2 administered by subcutaneous pellets causes local inflammation and systemic bone loss: a model for inflammation-induced bone disease.

The effects of prostaglandin E2 (PGE2) given in controlled-release pellets or by daily sc injection for 21 days on mineral homeostasis and bone histomorphometry were compared in 7-week-old female rats. Sham operation and ovariectomy were performed at the beginning of the studies. In experiment 1, 7.5 mg PGE2 or drug-free, controlled-release pellets were implanted sc at the back of the neck on day 7. In experiment 2, 3 mg/kg body weight of PGE2 or vehicle was injected sc daily beginning on day 7. The animals were sacrificed on day 28 of the two experiments, and the tibiae were removed for histomorphometric analysis of the diaphysis and metaphysis. When administered by pellets in experiment 1, PGE2 lowered serum 1,25-dihydroxyvitamin D and did not influence weight gain, serum calcium, phosphorus, or magnesium, cross-sectional or medullary areas, periosteal bone formation and apposition rates, endosteal bone formation and apposition rates, or endosteal tetracycline-labeled perimeter. PGE2 lowered cancellous bone area and cancellous bone perimeter in both the sham-operated and ovariectomized rats. In contrast, when administered by sc injection in experiment 2, PGE2 reduced weight gain, increased serum magnesium, increased cortical area, and reduced medullary area without changing cross-sectional area, increased periosteal bone formation and apposition rates and endosteal bone and apposition rates, did not alter endosteal tetracycline-labeled perimeter, and increased cancellous bone area and cancellous bone perimeter in both sham-operated and ovariectomized animals. PGE2 produced local inflammation when given by pellets, and the serum concentration of 13,14-dihydro-15-ketoprostaglandin E2, the major metabolite of PGE2, increased when PGE2 was given by sc injection but not when administered by pellets. Thus, PGE2 given sc by controlled-release pellets (1) produces local inflammation and systemic bone loss without increasing PGE2 systemically and (2) provides a model for inflammation-induced loss of cancellous bone. The results also indicate that the pellet is not a valid means for the delivery of PGE2 to the general circulation.

Evidence of a probable role for 25-hydroxyvitamin D in the regulation of human calcium metabolism.

1,25-Dihydroxyvitamin D [1,25-(OH)2D] is the principal mediator of the biologic effects of vitamin D. We showed previously that obese white subjects have low serum vitamin D and 25-hydroxyvitamin D (25-OHD) with increased serum-immunoreactive parathyroid hormone (PTH) and 1,25-(OH)2D, low urinary calcium, and increased urinary cyclic adenosine 3',5'-monophosphate (cyclic AMP) compared with nonobese white individuals. To determine whether 25-OHD modulates calcium metabolism, the effects of 25-OHD3, 40-100 micrograms/day for 9 days, were compared in seven obese and seven nonobese white subjects who were between the ages of 20 and 34 years. Each of them was hospitalized on a metabolic ward and given a constant daily diet that contained 400 mg calcium, 900 mg phosphate, and 18 mEq magnesium. Whereas 25-OHD3 increased mean serum 25-OHD from 7 +/- 1 to 37 +/- 5 ng/ml (P less than 0.01) and urinary calcium from 102 +/- 18 to 146 +/- 17 mg/day (P less than 0.001) and decreased mean serum 1,25-(OH)2D from 40 +/- 2 to 28 +/- 2 pg/ml (P less than 0.01) and urinary cyclic AMP from 3.23 +/- 0.57 to 2.00 +/- 0.17 nM/dl GF (P less than 0.05), it did not change mean serum calcium, ionized calcium, phosphate, magnesium, immunoreactive PTH or urinary phosphate, or creatinine clearance in the obese subjects. In contrast, 25-OHD3 increased mean serum 25-OHD from 16 +/- 1 to 46 +/- 4 pg/ml (P less than 0.001) but did not alter mean serum 1,25-(OH)2D or urinary calcium or cyclic AMP in the nonobese subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Enhancement of parathyroid hormone-responsive renal cortical adenylate cyclase activity by a cytosol protein activator from rat reticulocytes.

The effects of the cytosol activator protein obtained from rat reticulocytes (RCAP) were investigated in a heterologous membrane system--partially purified cell membranes from dog renal cortex. RCAP enhanced the response of dog renal cortical adenylate cyclase to bovine parathyroid hormone (1-34) [bPTH (1-34)] from two- to three-fold. RCAP also enhanced the response to 5 microM arginine vasopressin, 10 microM glucagon, and 10 microM isoproterenol. Analysis of double-reciprocal plots of substrate concentration and enzyme activity indicated that bPTH (1-34) alone and together with RCAP increased the Vmax of the adenylate cyclase enzyme and did not alter the apparent Km of the enzyme for MgATP. Membranes from dog renal cortex contain 42K and 39K proteins that are ADP-ribosylated by cholera toxin and pertussis toxin, respectively, and appear to be the stimulatory (Ns) and inhibitory (Ni) guanine nucleotide binding proteins described in many other hormone-responsive membrane preparations. Similar to its effects in rat reticulocytes, RCAP inhibited ADP-ribosylation of Ns and enhanced ADP-ribosylation of Ni. The muscarinic agonist, carbachol, inhibited PTH-responsive adenylate cyclase activity in dog renal cortical membranes and this inhibition was reversed by RCAP. These results indicate that RCAP enhances stimulation of adenylate cyclase by a variety of hormones in a heterologous membrane preparation and supports the hypothesis that RCAP's site of action is common to all adenylate cyclase systems. RCAP may facilitate coupling between Ns and the catalytic unit of adenylate cyclase by a pertussis toxin-like effect to inactivate Ni. The dual effects of RCAP upon ADP-ribosylation of Ni and Ns alpha subunits suggest that a binding site for RCAP may exist at a site of homology between Ns alpha and Ni alpha.

Oral lesions among women living with or at risk for HIV infection. HIV Epidemiology Research Study (HERS) Group.

PURPOSE: Our objectives were to compare the prevalence of oropharyngeal mucosal lesions among human immunodeficiency virus (HIV) seropositive and demographically similar seronegative women, and to determine the association of oral lesions with immunosuppression, substance abuse, use of medications, and utilization of dental services. POPULATION AND METHODS: Participants in a multicenter, longitudinal cohort study of HIV infection in women were evaluated at baseline by interview, physical examination, and laboratory studies. RESULTS: Oropharyngeal pathology was found in 40% of seropositive and 23% of seronegative women. Oral candidiasis was identified in 15% of seropositive and 3% of seronegative women. Among seropositive women, history of previous oral candidiasis, lower CD4 lymphocyte counts, and current antibiotic use were associated with oral candidiasis. Hairy leukoplakia was identified in 5% of seropositive women and was significantly associated with lower CD4 lymphocyte counts. Gingival erythema and ulcerative gingivitis were found in 23% of participants overall, but were unrelated to HIV serostatus or CD4 lymphocyte count. Substance abuse, lack of dental care, and African-American race were associated with gingival pathology. CONCLUSION: The high prevalence of oral lesions among HIV seropositive and at-risk seronegative women underscores the need for routine oral examination and targeted treatment of this population.

Aseptic transgressions among surgeons and anesthesiologists: a quantitative study.

The extent of compliance with 44 specific aseptic precautions by 18 surgeons and ten anesthesiologists was recorded during a series of 36 clean herniorrhaphies. Anesthesiologists as a group had an aseptic infraction rate nearly twice that of the surgeons, but a relatively small number in each group was responsible for most of the transgressions observed. The most frequent aseptic breaks involved scrubbing techniques (32.4% infraction rate) followed by dress and preparation breaks (12.9% infraction rate). Once physicians were inside the operating room and working, the infraction rate dropped considerably. The number of clinical wound infections observed (two) was too small to draw any conclusions about the association between asepsis and infection.

Natural history of Giardia lamblia and Cryptosporidium infections in a cohort of Israeli Bedouin infants: a study of a population in transition.

The natural history of Giardia lamblia and Cryptosporidium infections were determined in a cohort of 164 Bedouin children, from a population not previously studied, which is in transition from nomadism to a settled life style. Stools were sampled monthly from birth to two years of age and at all diarrhea episodes. The risk of infection with G. lamblia and Cryptosporidium infection by age two was 91.5% and 48.8%, respectively. Cryptosporidium prevalence was 3-4% at all ages, whereas G. lamblia prevalence was > 30% after age one. Giardia lamblia and Cryptosporidium asymptomatic detection rates were high, 28.5% and 1.6%, respectively. Detection of G. lamblia was higher in diarrhea episode samples obtained before six months of age, but after that age and overall, the detection was lower than in nondiarrhea samples (odds ratio [OR] = 0.8, 95% confidence interval [CI] = 0.7-0.9, P < 0.05). Detection rates of C. parvum were higher in episode-related samples in all age groups (OR = 2.8, 95% CI = 1.9-4.2, P < 0.05) and infections in boys were more frequently symptomatic than in girls. While G. lamblia does not appear to be a consistent pathogen in this population where it is hyperendemic, Cryptosporidium has been shown to be an important cause of diarrhea in young children in the community.

Microbial contamination associated with routine aseptic practice.

We have studied the rate of fortuitous contamination associated with routine aseptic technique under operational conditions. Stainless steel strips, as simulators of surgical instruments, were contained in sterilized surgical packs and assayed by nursing personnel during surgical and other invasive procedures at three different hospitals. The rates of contamination observed for the 36 investigators ranged from 0% to 11.3%, with an overall rate of 2.7%. Assays conducted in a clean room environment, under conditions approaching industrial sterility standards, showed a contamination rate of 0.16%. We concluded that aseptic practices, as routinely performed without any noticeable breaks or transgressions, do not guarantee sterility. The concept of surgical sterility implies low level, but measurable, microbial contamination.

Nursing home admission risk and the cost-effectiveness of community-based long-term care: a framework for analysis.

The relationship of prior risk of nursing home entry among applicants for community-based long-term care (CB/LTC) services to cost-effective admission decisions is investigated using decision analytic techniques. It is shown that using such evaluation criteria as have predominated in the major CB/LTC demonstrations, the necessary minimum level of prior risk is well above that typical of those actually enrolled. It is further shown that the remedy usually proposed, increasing the rigor and accuracy of enrollment screening, is unlikely to be of much practical effect. A case can be made, however, for defining the benefits of CB/LTC more broadly, in which case it may become cost-effective to enroll lower-risk applicants.

The effect of a support and education program on stress and burden among family caregivers to frail elderly persons.

An eight-week professionally guided caregiver support group program was found to produce statistically significant reductions in anxiety, depression, and sense of burden among family caregivers to frail elderly persons living in the community. Effects were weaker four months after the intervention ended than immediately after, but reductions in anxiety and depression were still evident.

The cost-effectiveness of community services in a frail elderly population.

We use an integrated model incorporating simple principles of decision analysis and marginal cost analysis to discuss cost-effectiveness of community long-term care services as a substitute for nursing home care. By taking individuals as the unit of analysis and analyzing different types of community services separately, the model defines the targeting issue precisely and permits key policy parameters to be estimated empirically. When applied to data from the National Long Term Care Channeling Demonstration, 41% of those screened into the control group were found to have some potential for net long-term care cost reduction through program services.

Premature institutionalization among the rural elderly in Arizona.

Rural areas of the United States, compared with urban areas, exhibit a scarcity of resources and programs designed to provide health and supportive services to impaired elderly persons living in the community. Furthermore, recent research has indicated that informal, familial support for the rural elderly has become increasingly attenuated because of such factors as outmigration of younger family members. Under these circumstances, there is reason for concern that a lack of available supportive services to help impaired rural elderly persons remain in the community may in effect drive them prematurely into nursing homes. In Arizona we have found that, consistent with such a process, elderly nursing home patients in rural areas tend on the average to be significantly less impaired in most areas of functional capacity, and younger at time of entry, than elderly nursing home patients in urban areas. This pattern remains when various possible confounding effects are statistically controlled.

Can home care services achieve cost savings in long-term care for older people?

OBJECTIVE: To determine whether efficient allocation of home care services can produce net long-term care cost savings. METHODS: Hazard function analysis and nonlinear mathematical programming. RESULTS: Optimal allocation of home care services resulted in a 10% net reduction in overall long-term care costs for the frail older population served by the National Long-Term Care (Channeling) Demonstration, in contrast to the 12% net cost increase produced by the demonstration intervention itself. DISCUSSION: Our findings suggest that the long-sought goal of overall cost-neutrality or even cost-savings through reducing nursing home use sufficiently to more than offset home care costs is technically feasible, but requires tighter targeting of services and a more medically oriented service mix than major home care demonstrations have implemented to date.