Implementation of a multidisciplinary guideline improves preterm infant admission temperatures.

BACKGROUND: Hypothermia is a common problem in preterm infants immediately following delivery.Local problem:The rate of admission hypothermia in our neonatal intensive care unit (NICU) was above the rate of comparable NICUs in the Vermont Oxford Network. METHODS: To reduce the rate of preterm admission hypothermia, a quality improvement (QI) project was implemented, utilizing the plan-do-study-act (PDSA) methodology. A guideline for delivery room thermoregulation management in <35-week infants at the University of Virginia was created and put into practice by a multidisciplinary team. INTERVENTIONS: Clinical practice changes in the guideline included: increasing operating room temperatures, obtaining a 10-min axillary temperature, using an exothermic mattress for all infants <35 weeks, and using a polyethylene wrap for infants <32 weeks. RESULTS: The baseline rate of hypothermia (<36.5 °CC) was 63%. Three PDSA cycles data were completed on 168 consecutive preterm births. The post-implementation rate of hypothermia (<36.5 °C) was reduced to 30% (P<0.001). The incidence of moderate hypothermia (< 36 °C) was reduced from a baseline of 29% to a rate of 9% (P<0.001). CONCLUSION: Use of a multidisciplinary guideline to increase preterm NICU admission temperatures resulted in a decrease in hypothermic infants.

Eating and arterial endothelial function: a meta-analysis of the acute effects of meal consumption on flow-mediated dilation.

Given that endothelial dysfunction precedes atherosclerotic cardiovascular disease, exploring the parameters that modify postprandial flow-mediated dilation (FMD) is important for public health. The objectives of the study are to estimate the population effect of meal ingestion on FMD and to determine how the effect varied based on patient characteristics and modifiable methodological features. Articles published before June 2015 were located using MEDLINE, PubMed and Web of Science. One hundred fifty-four effects were derived from 78 articles involving 2,548 subjects were selected. Included articles required measurement of FMD in adults before and after meal ingestion. Effects were analysed using an unstandardized mean gain random effects model, and significant moderators were analysed using meta-regression. Meal consumption significantly reduced FMD by a heterogeneous mean effect size delta (Δ) of -2.03 (95% CI: [-2.28, -1.77]), an ~2% reduction in FMD. FMD reductions were larger among normal weight individuals, males, those with a cardio-metabolic disorder, those with elevated baseline FMD, and individuals with impaired glucose tolerance at baseline. Macronutrient meal ingestion significantly reduced FMD, an effect that was moderated by body mass index, sex and two-way interactions between disease status and both baseline FMD and baseline blood glucose levels.

Pseudoexfoliation and sensorineural hearing loss.

AIMS: There is increasing evidence that pseudoexfoliation (PXF) not only affects ocular anterior segment structures, but may also be a systemic disease. This study was undertaken to assess the relationship between PXF and sensorineural hearing loss. METHODS: Patients with PXF were identified from hospital records and underwent complete ocular examination. The sum of pure-tone hearing thresholds measured at 1, 2 and 3 kHz (HTL1,2,3) in each ear was compared with the ISO 7029 standard sex-matched, median age-associated hearing loss summed over the same frequencies (AAHL1,2,3). The proportion of ears with thresholds higher than the ISO 7029 median AAHL1,2,3 on the same side as eyes without PXF was compared with the proportion of ears ipsilateral to eyes with PXF but without glaucoma and similarly the proportion of ears on the same side as eyes with PXF and glaucoma. RESULTS: In total, 69 patients were studied, of whom 39 were male (56.5%). The mean age of the male patients was 75.8 years, while that of the female group was 75.1 years. All patients had PXF affecting at least one eye. Overall 101 ears (73.7%) had a higher HTL1,2,3 than the ISO 7029 median AAHL1,2,3 which included 56 ears of 78 in the male group (71.8%) and 45 ears of 59 in the female group (76.3%). There was no significant difference between the proportion of ears with HTL1,2,3 higher than the ISO 7029 median AAHL1,2,3 on the same side as eyes without PXF, with PXF but not glaucoma and with PXF and glaucoma, in either the male or female groups. CONCLUSIONS: A large proportion of patients with PXF have sensorineural hearing loss in comparison to age-matched controls, regardless of whether or not there is associated glaucoma. This finding supports the theory that PXF may be a systemic condition.

Protein tyrosine phosphatase PTP1 negatively regulates Dictyostelium STATa and is required for proper cell-type proportioning.

The protein tyrosine phosphatase PTP1, which mediates reversible phosphorylation on tyrosine, has been shown to play an important regulatory role during Dictyostelium development. Mutants lacking PTP1 develop more rapidly than normal, while strains that overexpress PTP1 display aberrant morphology. However, the signalling pathways involved have not been characterised. In reexamining these strains, we have found that there is an inverse correlation between levels of PTP1 activity, the extent of tyrosine phosphorylation on Dictyostelium STATa after treatment with cAMP, and the proportion of the slug population exhibiting STATa nuclear enrichment in vivo. This suggests that PTP1 acts to attenuate the tyrosine phosphorylation of STATa and downstream STATa-mediated pathways. Consistent with this, we show that when PTP1 is overexpressed, there is increased expression of a prestalk cell marker at the slug posterior, a phenocopy of STATa null slugs. In ptp1 null strains, STATa tyrosine phosphorylation and nuclear enrichment in the slug anterior is increased. There is also a change in the prestalk to prespore cell ratio. Synergy experiments suggest that this is due to a cell-autonomous defect in forming the subset of prespore cells that are located in the anterior prespore region.

Testicular microlithiasis: prevalence and tumor risk in a population referred for scrotal sonography.

OBJECTIVE: Considerable accrued evidence points to an association between testicular microlithiasis, intratubular germ cell neoplasia, and testicular tumor. This study assesses both the prevalence of testicular microlithiasis revealed on sonography in a referred population and the concurrent tumor risk. MATERIALS AND METHODS: Over a 32-month period (April 1996 through November 1998), 4892 scrotal sonographic examinations were performed in 4819 patients at four referral centers. All patients underwent high-resolution (7- to 10-MHz) imaging. Using a computerized word search (n = 4102; testicular microlithiasis, calcification, microliths, calcific foci, tumor, neoplasm, cancer, hyperecho, hypoecho, heterogen, and carcinoma) and manual retrieval (n = 790), cases of tumor, testicular microlithiasis (>5 microliths per sonogram), and testicular microlithiasis plus tumor were pulled and retrospectively reviewed. The presence and type of tumor were confirmed at histology after orchidectomy. RESULTS: Fifty-four tumors were found among 4892 scrotal sonograms (28 seminomas, 14 teratomas, 8 mixed germ cell tumors, 2 Leydig cell tumors, and 2 non-Hodgkin's lymphomas). Testicular microlithiasis was present in 33 patients, giving a prevalence of 0.68%. Concurrent tumor and testicular microlithiasis were detected in seven patients, a relative risk of tumor in testicular microlithiasis was 21.6-fold (95% confidence limits: 10. 6-fold, 44.2-fold). In one patient with testicular microlithiasis, a previous orchidectomy for mixed germ cell tumor had been performed (not included in the relative risk calculation). CONCLUSION: In a referred population of 4819 patients the prevalence of testicular microlithiasis was 0.68% and the relative risk of concurrent tumor was 21.6-fold. Sonographic surveillance of testicular microlithiasis cases for tumor is mandatory.

Evidence that the Dictyostelium Dd-STATa protein is a repressor that regulates commitment to stalk cell differentiation and is also required for efficient chemotaxis.

Dd-STATa is a structural and functional homologue of the metazoan STAT (Signal Transducer and Activator of Transcription) proteins. We show that Dd-STATa null cells exhibit several distinct developmental phenotypes. The aggregation of Dd-STATa null cells is delayed and they chemotax slowly to a cyclic AMP source, suggesting a role for Dd-STATa in these early processes. In Dd-STATa null strains, slug-like structures are formed but they have an aberrant pattern of gene expression. In such slugs, ecmB/lacZ, a marker that is normally specific for cells on the stalk cell differentiation pathway, is expressed throughout the prestalk region. Stalk cell differentiation in Dictyostelium has been proposed to be under negative control, mediated by repressor elements present in the promoters of stalk cell-specific genes. Dd-STATa binds these repressor elements in vitro and the ectopic expression of ecmB/lacZ in the null strain provides in vivo evidence that Dd-STATa is the repressor protein that regulates commitment to stalk cell differentiation. Dd-STATa null cells display aberrant behavior in a monolayer assay wherein stalk cell differentiation is induced using the stalk cell morphogen DIF. The ecmB gene, a general marker for stalk cell differentiation, is greatly overinduced by DIF in Dd-STATa null cells. Also, Dd-STATa null cells are hypersensitive to DIF for expression of ST/lacZ, a marker for the earliest stages in the differentiation of one of the stalk cell sub-types. We suggest that both these manifestations of DIF hypersensitivity in the null strain result from the balance between activation and repression of the promoter elements being tipped in favor of activation when the repressor is absent. Paradoxically, although Dd-STATa null cells are hypersensitive to the inducing effects of DIF and readily form stalk cells in monolayer assay, the Dd-STATa null cells show little or no terminal stalk cell differentiation within the slug. Dd-STATa null slugs remain developmentally arrested for several days before forming very small spore masses supported by a column of apparently undifferentiated cells. Thus, complete stalk cell differentiation appears to require at least two events: a commitment step, whereby the repression exerted by Dd-STATa is lifted, and a second step that is blocked in a Dd-STATa null organism. This latter step may involve extracellular cAMP, a known repressor of stalk cell differentiation, because Dd-STATa null cells are abnormally sensitive to the inhibitory effects of extracellular cyclic AMP.

Effects of cold exposure on estrous behavior and neural estrogen receptor in Syrian hamsters.

Two experiments examined the effects of 72-h exposure to reduced environmental temperature (5 degrees C) on steroid-induced estrous behavior and neural estrogen-receptor immunoreactivity (ERIR) in ovariectomized Syrian hamsters. Cold exposure significantly inhibited sexual receptivity induced by sequential injections of estradiol benzoate (2.5 microg) and progesterone (500 microg), but only if the animals were not permitted to overeat (limited to 110% of ad lib intake at 22 degrees C). The suppression of sexual receptivity was accompanied by decreases in the number of detectable ERIR cells in the ventromedial hypothalamus (VMH) and by increases in the number of ERIR cells in the medial preoptic area (mPOA). The cold-induced decreases in estrous behavior and in VMH ERIR cells were prevented by lesions of the area postrema (AP), but AP lesions did not prevent the increases in mPOA ERIR cells. Thus, cold exposure mimics the effects of treatment with metabolic inhibitors, experimental diabetes, food deprivation, and insulin-induced fattening on these endpoints. These findings are consistent with the hypothesis that dwelling in the cold affects reproduction indirectly via its actions on metabolic fuel availability, rather than by acting directly on neuroendocrine processes.

Signalling pathways that direct prestalk and stalk cell differentiation in Dictyostelium.

Prestalk cell differentiation in Dictyostelium is induced by DIF and two DIF-induced genes, ecmA and ecmB, have revealed the existence of multiple prestalk and stalk cell sub-types. These different sub-types are defined by the pattern of expression of subfragments derived from the ecmA and ecmB promoters. These markers have been utilised in three ways; for fate mapping in vivo, to investigate the molecular mechanisms underlying DIF signalling and to explore the relative requirement for DIF and other signalling molecules for prestalk and stalk cell differentiation in vitro. The heterogeneity of the prestalk and stalk populations seems to be reflected in differences in the cell signalling pathways that they utilise.

Developmentally and spatially regulated activation of a Dictyostelium STAT protein by a serpentine receptor.

Dd-STAT, the protein that in part controls Dictyostelium stalk cell differentiation, is a structural and functional homolog of metazoan signal transducers and activators of transcription (STATs). Although present during growth and throughout development, Dd-STAT's tyrosine phosphorylation and nuclear localization are developmentally and spatially regulated. Prior to late aggregation, Dd-STAT is not tyrosine phosphorylated and is not selectively localized in the nucleus. During mound formation, the time at which cell-type specific gene expression initiates, Dd-STAT becomes tyrosine phosphorylated and translocates into the nuclei of all cells. The tyrosine phosphorylation and nuclear localization of Dd-STAT are induced very rapidly by extracellular cAMP through the serpentine cAMP receptor cAR1, with Dd-STAT tyrosine phosphorylation being detectable within 10 s of stimulation. This activation is independent of the only known Gbeta subunit, suggesting that it may be G-protein independent. Nuclear enrichment of Dd-STAT is selectively maintained within the sub-population of prestalk cells that form the tip, the organizing center of the slug, but is lost in most of the other cells of the slug. This spatial patterning of Dd-STAT nuclear localization is consistent with its known role as a negative regulator of stalk-cell differentiation.

Estrogen receptors are essential for female sexual receptivity.

One of the most important, robust and evolutionarily conserved functions for neural estrogen receptor (ER) is as a mediator of female sexual behavior. Using homozygotic ER knockout (ERKO) mice we tested the hypothesis that ER controls female receptivity. Females with either two normal copies of the ER gene (wild-types), or an insertational disruption (knockouts) of the ER were ovariectomized. Each female was treated with 17 beta-estradiol (EB) alone, and with EB in combination with progesterone, prior to tests for behavioral receptivity. Under both hormonal conditions female ERKO mice did not display sexual receptivity whereas wild-type litter-mates were receptive to males. Male behavior indicated that females of both genotypes were equally attractive. Brain tissues were examined with immunocytochemical methods showed that ERKOs had greatly reduced levels of ER immunoreactivity in hypothalamus. In sum, the data show that ER is required for the display of sexual receptivity, but is not essential for female attractivity.

cAMP-dependent protein kinase is required for the expression of a gene specifically expressed in Dictyostelium prestalk cells.

In the Dictyostelium slug there are two types of prestalk cells, pstA cells and pstO cells, that differ in their ability to utilize the distal and proximal parts of the promoter of ecmA, a gene that is specifically expressed in prestalk cells. When Rm, a dominant inhibitory form of the regulatory subunit of cAMP-dependent protein kinase (PKA), is expressed under the control of the complete promoter of the ecmA gene (in a construct termed ecmAO:Rm) development proceeds to the slug stage. Although able to form small but outwardly normal slugs, ecmAO:Rm cells are defective in prestalk cell differentiation. In ecmAO:Rm cells, the induction of pstA- and pstO-specific gene expression by the stalk cell inducer DIF is greatly inhibited. Paradoxically, a very large fraction of the cells in an ecmAO:Rm slug show evidence of once having expressed the ecmA and ecmO prestalk markers. However, we present evidence that this is due to abortive prestalk cell differentiation that terminates when sufficient Rm protein has accumulated to block PKA activity. This results in regulative transdifferentiation of prespore cells to form prestalk cells. During their transitory period as prestalk cells the ecmAO:Rm cells coexpress both the ecmA and ecmO markers, indicating a possible link between PKA activity and divergence of the two prestalk cell subtypes. Finally, we show that the level of the DNA binding activity believed to lie at the end of the DIF signal transduction pathway is reduced in ecmAO:Rm slugs.

Evidence that a combined activator-repressor protein regulates Dictyostelium stalk cell differentiation.

The ecmA gene is expressed in Dictyostelium prestalk cells and is inducible by differentiation-inducing factor (DIF), a low-molecular-weight lipophilic substance. The ecmB gene is expressed in stalk cells and is under negative control by two repressor elements. Each repressor element contains two copies of the sequence TTGA in an inverted relative orientation. There are activator elements in the ecmA promoter that also contain two TTGA sequences, but in the same relative orientation. Gel retardation assays suggest that the same protein binds to the ecmB repressor and the ecmA activator. We propose that DIF induces prestalk cell differentiation by activating this protein and that the protein also binds to the promoters of stalk-specific genes, acting as a repressor that holds cells in the prestalk state until culmination is triggered.

Evidence for positional differentiation of prestalk cells and for a morphogenetic gradient in Dictyostelium.

We present evidence that Dictyostelium slug tip cells, the pstA cells, may arise by positional differentiation, but at a site remote from that which they will eventually occupy. When first detectable, the pstA cells form a peripheral ring surrounding the other prestalk cell subtype, the pstO cells, but subsequently move above the pstO cells to form the tip. Because pstA cell differentiation requires a 10-fold higher concentration of differentiation-inducing factor, the stalk cell inducer, the initial patterning seems likely to reflect the existence of a morphogenetic gradient. The subsequent redistribution of the two cell types is explicable by their different rates of chemotaxis to cyclic AMP. These results help reconcile the two apparently opposing views of pattern formation in Dictyostelium, that there is positional differentiation and that pattern formation occurs by cell sorting.

Clinical, ultrasound and hormonal markers of androgenicity in acne vulgaris.

Androgenic stimulation of sebaceous glands is an important factor in the development of acne. We examined 36 females (aged 14-34 years), selected because none had received oral contraceptives, anti-androgen therapy, or systemic antibiotics during the previous year, or isotretinoin therapy, prior to their participation in the study. Subjects were divided into groups on the basis of acne severity, as follows: physiological, mild and moderate. Only two patients had polycystic ovaries on ultrasound examination. Seven patients had irregular menses; none had evidence of hirsutism. We found that the severity of acne, based on the acne grade, was highly correlated with the inflammatory lesion count, and less correlated with the sebum excretion rate. Either acne grade or inflammatory lesion count could be related to some of the five androgenic hormone determinants; free testosterone (TESTOS), delta 4 androstenedione (DELTA 4), sex hormone binding globulin (SHBG), dehydroepiandrostenedione sulphate (DHEAS) and dihydrotestosterone (DHT). Multiple linear regression analysis determined the best model for predicting ACNE scores as involving DELTA 4 and DHEAS (positive effects), and SHBG (negative effect), P < 0.005, R2 = 0.36). In none of the patients were the levels of DHEAS or SHBG outside the normal range. The findings in the two patients with polycystic ovaries did not differ significantly from those in the remainder of the patients.

Adherence of bacteria to intraocular lenses: a prospective study.

AIMS: The study was designed to investigate the bacterial flora of the operating field during routine cataract surgery and the source of intraocular lens contamination during the surgery. METHODS: The normal flora of the external eye and fornices of 17 patients undergoing selective cataract surgery was determined preoperatively. Swabs taken from the eyelid surface and lashes showed coagulase negative staphylococci (CNS) in 90%, Propionibacterium acnes in 62%, Corynebacterium sp in 18%, and Peptostreptococcus in 3% of the patients. The lower fornices of 70% had CNS, 47% P acnes, 6% Staphylococcus aureus, 6% Corynebacterium sp, and 6% Candida. RESULTS: A sterile PMMA intraocular lens was touched on the upper bulbar conjunctiva immediately before the surgery. Eighty two per cent of lenses grew CNS, 18% P acnes, 18% Bacillus sp, 12% S aureus, and 6% Corynebacterium sp. A second sterile PMMA intraocular lens was left on the drape and near the eye during surgery. Forty seven per cent of these cultured CNS, 12% Corynebacterium sp, and 6% Bacillus sp. A high count of bacteria in the operating field, especially CNS and P acnes can contribute to postoperative inflammation and endophthalmitis. CONCLUSION: Special measures are needed before and during the surgery to reduce the chance of intraocular inoculation of these bacteria. Use of proper culture media and techniques are necessary to identify these organisms, especially anaerobes, in postoperative inflammation.

A team approach to geriatric case management.

Providing high-quality, comprehensive care for elderly Americans is becoming increasingly challenging because of the aging of society, the shortage of primary care physicians, and rising health care costs. These trends are encouraging health care delivery systems to adopt alternative models of patient care. This article reports on one such model, the complementary practice model, which incorporates a team approach to geriatric case management. The complementary practice model targets the frail elderly who are near the end of life, or are at highest risk for either hospitalization or cognitive decline. It includes a diverse, multidisciplinary team to provide patient care by involving the patient, family, physician, nurse practitioner, social worker, and registered nurse as core team members. This team approach assesses and identifies patients' problems, utilizes the expertise of multiple health care disciplines, and encourages patients and families to be active participants in developing and implementing the case management plan.

Patterns of cell movement within the Dictyostelium slug revealed by cell type-specific, surface labeling of living cells.

There are cells scattered in the rear, prespore region of the Dictyostelium slug that share many of the properties of the prestalk cells and that are therefore called anterior-like cells (ALCs). By placing the gene encoding a cell surface protein under the control of an ALC-specific promoter and immunologically labeling the living cells, we analyze the movement of ALCs within the slug. There is a posterior to anterior cellular flow, and the ALCs change their movement pattern as they enter the prestalk zone. Prestalk cells are periodically shed from the migrating slug. They must be replaced if the correct ratio of prestalk to prespore cells is to be maintained, and we present evidence for the transdifferentiation of prespore into prestalk cells, with ALCs functioning as intermediates in the transition. The slug has, therefore, a surprisingly dynamic structure, both with respect to cellular differentiation and cell movement.