Multicenter Evaluation of the Novel ETEST Fosfomycin for Antimicrobial Susceptibility Testing of Enterobacterales, Enterococcus faecalis, and Staphylococcus Species.

Fosfomycin is a phosphonic acid derivative active against a wide spectrum of Gram-positive and Gram-negative pathogens. It is used for the treatment of uncomplicated urinary tract infections (uUTI) or severe infections by oral or intravenous (i.v.) administration. In order to improve its performance and robustness, the fosfomycin strip, an antibiotic gradient diffusion strip, was redeveloped and evaluated in the multicenter study summarized in this paper. ETEST fosfomycin (ETEST FO) clinical performance was evaluated by three study sites on 152 Enterococcus faecalis, 100 Staphylococcus spp. and 330 Enterobacterales in comparison with the CLSI and EUCAST agar dilution reference method. Referring to FDA performance criteria, the ETEST FO achieved 91.0% of essential (EA) and 99.0% of categorical agreement (CA) for Escherichia coli. In addition, 98.0% EA and 93.4% CA were achieved for E. faecalis, with no very major errors (VME) or major errors (ME). According to EUCAST breakpoints for intravenous fosfomycin use, Enterobacterales and Staphylococcus spp. also met ISO acceptance criteria for EA and CA (EA 91.5%, 94.0%, respectively, and CA 98.0% for both). A VME rate of 8.8% was observed for Enterobacterales but the MICs were within EA. A trend to predict lower MICs for Citrobacter spp., E. coli and Salmonella enterica and to predict higher MICs for Klebsiella pneumoniae MICs was observed, while ETEST FO should not be used for Enterobacter cloacae, because of low EA and a high VME rate. The study results support the efficiency of the novel ETEST FO, making it an easy-to-handle tool as a substitute to the classical agar dilution method.

Radiosensitivity and transgenerational effects in non-human species.

The ALLIANCE working group on effects of ionising radiation on wildlife brings together European researchers to work on the topics of radiosensitivity and transgenerational effects in non-human biota. Differences in radiation sensitivity across species and phyla are poorly understood, but have important implications for understanding the overall effects of radiation and for radiation protection; for example, sensitive species may require special attention in monitoring and radiation protection, and differences in sensitivity between species also lead to overall effects at higher levels (community, ecosystem), since interactions between species can be altered. Hence, understanding the mechanisms of interspecies radiation sensitivity differences may help to clarify mechanisms underpinning intraspecies variation. Differences in sensitivity may only be revealed when organisms are exposed to ionising radiation over several generations. This issue of potential long-term or hereditary effects for both humans and wildlife exposed to low doses of ionising radiation is a major concern. Animal and plant studies suggest that gamma irradiation can lead to observable effects in the F1 generation that are not attributable to inheritance of a rare stable DNA mutation. Several studies have provided evidence of an increase in genomic instability detected in germ or somatic cells of F1 organisms from exposed F0 organisms. This can lead to induced radiosensitivity, and can result in phenotypic effects or lead to reproductive effects and teratogenesis. In particular, studies have been conducted to understand the possible role of epigenetic modifications, such as DNA methylation, histone modifications, or expression of non-coding RNAs in radiosensitivity, as well as in adaptation effects. As such, research using biological models in which the relative contribution of genetic and epigenetic processes can be elucidated is highly valuable.

Expanded prediction equations of human sweat loss and water needs.

The Institute of Medicine expressed a need for improved sweating rate (msw) prediction models that calculate hourly and daily water needs based on metabolic rate, clothing, and environment. More than 25 years ago, the original Shapiro prediction equation (OSE) was formulated as msw (g.m(-2).h(-1))=27.9.Ereq.(Emax)(-0.455), where Ereq is required evaporative heat loss and Emax is maximum evaporative power of the environment; OSE was developed for a limited set of environments, exposures times, and clothing systems. Recent evidence shows that OSE often overpredicts fluid needs. Our study developed a corrected OSE and a new msw prediction equation by using independent data sets from a wide range of environmental conditions, metabolic rates (rest to 500 observations) by using a variety of metabolic rates over a range of environmental conditions (ambient temperature, 15-46 degrees C; water vapor pressure, 0.27-4.45 kPa; wind speed, 0.4-2.5 m/s), clothing, and equipment combinations and durations (2-8 h). Data are expressed as grams per square meter per hour and were analyzed using fuzzy piecewise regression. OSE overpredicted sweating rates (P<0.003) compared with observed msw. Both the correction equation (OSEC), msw=147.exp (0.0012.OSE), and a new piecewise (PW) equation, msw=147+1.527.Ereq-0.87.Emax were derived, compared with OSE, and then cross-validated against independent data (21 males and 9 females; >200 observations). OSEC and PW were more accurate predictors of sweating rate (58 and 65% more accurate, P<0.01) and produced minimal error (standard error estimate<100 g.m(-2).h(-1)) for conditions both within and outside the original OSE domain of validity. The new equations provide for more accurate sweat predictions over a broader range of conditions with applications to public health, military, occupational, and sports medicine settings.

[Hospital infection control--beyond the hospital]. / Hygiène hospitatière--au-delà de l'hôpital.

Health care related infections are expensive untoward events, not only in terms of morbidity and mortality, but also cost. Prevention is essential, as well as limiting dissemination. Specify measures refer usually to hospital hygiene. However, health care tend to be provided more and more outside of the acute care hospital, with increasing complexity and thus risk for health care related infections. This risk varies according to patient's characteristics as well as environmental parameters. Consequently, it is essential to adapt preventive measures to situations such as home health care or nursing homes. We describe a model of regional organization for infection control in various health care settings.

Physiological responses to cold exposure in men: a disabled submarine study.

A disabled submarine (DISSUB) lacking power and/or environmental control will become cold, and the ambient air may become hypercapnic and hypoxic. This study examined if the combination of hypoxia, hypercapnia, and cold exposure would adversely affect thermoregulatory responses to acute cold exposure in survivors awaiting rescue. Seven male submariners (33 +/- 6 yrs) completed a series of cold-air tests (CAT) that consisted of 20-min at T(air) = 22 degrees C, followed by a linear decline (1 degrees C x min(-1)) in T(air) to 12 degrees C, which was then held constant for an additional 150-min. CAT were performed under normoxic, normocapnic conditions (D0), acute hypoxia (D1, 16.75% O2), after 4 days of chronic hypoxia, hypercapnia and cold (D5, 16.75% O2, 2.5% CO2, 4 degrees C), and hypoxia-only again (D8, 16.75% O2). The deltaTsk during CAT was larger (P < 0.05) on D0 (-5.2 degrees C), vs. D1 (-4.8 degrees C), D5 (-4.5 degrees C), and D8 (-4.4 degrees C). The change (relative to 0-min) in metabolic heat production (deltaM) at 20-min of CAT was lower (P < 0.05) on D1, D5, and D8, vs. D0, with no differences between D1, D5 and D8. DeltaM was not different among trials at any time point after 20-min. The mean body temperature threshold for the onset of shivering was lower on D1 (35.08 degrees C), D5 (34.85 degrees C), and D8 (34.69 degrees C), compared to D0 (36.01 degrees C). Changes in heat storage did not differ among trials and rectal temperature was not different in D0 vs. D1, D5, and D8. Thus, mild hypoxia (16.75% F1O2) impairs vasoconstrictor and initial shivering responses, but the addition of elevated F1CO2 and cold had no further effect. These thermoregulatory effector changes do not increase the risk for hypothermia in DISSUB survivors who are adequately clothed.

What is community? An evidence-based definition for participatory public health.

Increased emphasis on community collaboration indicates the need for consensus regarding the definition of community within public health. This study examined whether members of diverse US communities described community in similar ways. To identify strategies to support community collaboration in HIV vaccine trials, qualitative interviews were conducted with 25 African Americans in Durham, NC; 26 gay men in San Francisco, Calif; 25 injection drug users in Philadelphia, Pa; and 42 HIV vaccine researchers across the United States. Verbatim responses to the question "What does the word community mean to you?" were analyzed. Cluster analysis was used to identify similarities in the way community was described. A common definition of community emerged as a group of people with diverse characteristics who are linked by social ties, share common perspectives, and engage in joint action in geographical locations or settings. The participants differed in the emphasis they placed on particular elements of the definition. Community was defined similarly but experienced differently by people with diverse backgrounds. These results parallel similar social science findings and confirm the viability of a common definition for participatory public health.

Formation of furfurylthiol exhibiting a strong coffee aroma during oak barrel fermentation from furfural released by toasted staves.

Furfurylthiol (FFT) is formed in white wines during alcoholic fermentation in the barrel from the furfural released by toasted staves. The quantity of furfural released into the must has a decisive effect on the quantity of FFT in the finished wine. Wines fermented in new barrels thus contain larger quantities of FFT than those fermented in used barrels. Fermentation conditions favorable to an excess production of H(2)S (hydrogen sulfide) by the yeast promote the formation of this volatile thiol. The presence of this volatile thiol in white wines is, therefore, closely related to the yeast's sulfur metabolism.

A proposed model for load carriage on sloped terrain.

BACKGROUND: The purpose of this study was to develop a predictive model for uphill and downhill load carriage. Relative to level walking, net energy costs increase with uphill movement and decrease moving downhill. To simulate load carriage over complex terrain, a model must estimate the cost of downhill movement. The net cost of downhill movement is expected to reach a minimum value, then increase as work is required to maintain stability. Thus, downhill costs cannot be simply extrapolated from a linear relationship for uphill work. METHOD: Oxygen uptake (VO2) was measured for 16 subjects during test sessions which consisted of walking at 1.34 m x s(-1) on a single grade (-12%, -10%, -8%, -4%, -2%, 0%, +4%, +4%, +8% and +12%) with a 0, 9.1- or 18.1-kg load. RESULTS: No significant gender differences were found, therefore data were pooled. The minimum VO2 values occurred at -8% grade. CONCLUSION: Our model assumes that the total energy requirement (WT) is the sum of the cost of level walking (W(L)) plus the cost of vertical displacement (Wv) for the total mass (body plus load). For uphill work, Wv was calculated by multiplying the cost of vertical displacement by an efficiency factor. For downhill work, the cost of vertical displacement was modified by an exponential function of the slope angle. Values for level and negative slope walking with no load were compared with estimated values derived from two published studies to partially validate the negative model.

Thermal properties of handwear at varying altitudes.

BACKGROUND: Total handwear insulation (I(T)) is dependent on the rate of heat transfer in air through the skin-handwear interface, handwear layers, and the surface boundary air layer. As altitude increases, the corresponding decrease in air pressure reduces convective heat loss. As convective heat losses decline, I(T), which is inversely related to the rate of heat loss, should increase. Increasing air velocity also reduces the insulation (Ia) provided by the boundary layer. METHODS: The military issue test handwear, Light-duty glove (LD), Trigger-finger mitten (TF), and Arctic mitten (AM), were fitted over a biophysical hand model. Model surface temperatures were 25 degrees C, and air temperature was 10 degrees C. The handwear was tested at simulated altitudes of sea level (101 kPa), 2500 m (75 kPa) and 5000 m (54 kPa) in still air and at 5 m x s(-1). RESULTS: Overall, the effects of wind and altitude on I(T) were significant. Differences for I(T) between 0 and 5000 m were significant for LD and TF. Increases in I(T) greater than 10% are considered of sufficient magnitude to alter comfort sensation. CONCLUSIONS: Differences of that magnitude occurred most frequently between 0 and 5000 m. The present results are consistent with an increase in I(T) with increasing altitude. Changes in I(T) were greater in still air and for less insulated handwear where the contribution of Ia to I(T) was more important.

Heat strain evaluation of chemical protective garments.

BACKGROUND: The purpose of this study was to compare thermoregulatory and subjective responses of 12 test subjects (10 male, 2 female) wearing 5 different Joint Service Lightweight Integrated Suit Technology (JSLIST) prototype and 3 different currently fielded control chemical/ biological (CB) protective overgarments. METHODS: The overgarments were compared while subjects attempted to complete 100 min of moderate exercise (400 W) in an environmental chamber (35 degrees C/50% rh). Rectal temperature (Tre), skin temperature, heart rate, sweating rate, and test time, as well as subjective symptoms of heat illness were measured. Data were analyzed for times earlier than 100 min because subjects were not usually able to complete the 100-min trials. RESULTS: At 50 min, of the 3 controls, the Army/Air Force Battledress Overgarment (BDO) imposed significantly greater heat strain (indicated by Tre 37.90 degrees C) than the Marine Saratoga (SAR) (Tre 37.68 degrees C) and Navy Chemical Protective Overgarment (CPO) (Tre 37.69 degrees C). The JSLIST prototype garments imposed heat strain (50 min Tre 37.73-37.86 degrees C) as well as subjective perception of heat strain, that ranged between the warmest and coolest controls. CONCLUSIONS: In the environmental and exercise test conditions of this study, we did not find the five JSLIST overgarments to be consistently different from one another. Subjects in the control garments were and felt generally warmer (BDO) or cooler (SAR, CPO) than in the JSLIST prototype garments.

A powerful aromatic volatile thiol, 2-furanmethanethiol, exhibiting roast coffee aroma in wines made from several Vitis vinifera grape varieties.

The chemical compound 2-furanmethanethiol (2FM), with a strong roast coffee aroma, has been identified in sweet white wines made from the Petit manseng grape variety, and in certain red Bordeaux wines (made from the Merlot, Cabernet franc, and Cabernet sauvignon grape varieties). This was done by extracting specific volatile thiols using p-hydroxymercuribenzoate. The 2FM has also been found in toasted oak used in barrel-making. All the Petit manseng sweet white wines and some of the red Bordeaux wines analyzed contained between a few ng/L and several dozen ng/L of 2FM. Taking into account its very low perception threshold (0.4 ng/L in a model hydro alcoholic environment), 2FM could therefore contribute to the roast coffee aroma of certain wines.

Potent and selective non-peptidic inhibitors of endothelin-converting enzyme-1 with sustained duration of action.

Potent and selective non-peptidic inhibitors of human endothelin-converting enzyme-1 (ECE-1) have been designed as potential modulators of endothelin (ET-1) production in vivo. Because of its unique structural characteristics and long duration of action in vivo, the dual ECE-1 and neutral endopeptidase 24.11 (NEP) inhibitor, CGS 26303, was selected as an attractive lead for further optimization of potency and selectivity. Replacement of the P(1)' biphenyl substituent of CGS 26303 by a conformationally restricted 3-dibenzofuranyl group led to more potent and more selective ECE-1 inhibitors, such as the tetrazole 27. The remarkable effect of this P(1)' modification allowed for the first time phosphonomethylcarboxylic acids, such as 29, to display both potent (IC(50) = 22 nM) and selective (104-fold vs NEP) ECE-1 inhibition. Chemoenzymatic syntheses of the new alpha-amino acid (S)-3-dibenzofuran-3-ylalanine intermediate were developed, and improved procedures to generate substituted alpha-aminoalkylphosphonic acids were devised to support the production of various analogues. Although additional gains in intrinsic ECE-1 inhibitory potency could occasionally be achieved by addition of a P(1) side chain, these compounds (e.g. 43a) showed poor functional activity in vivo in the big ET-1 pressor test. Phosphonoalkyl dipeptides featuring 3-dibenzofuranyl groups in both the P(1)' and P(2)' positions were also very potent ECE-1 inhibitors, albeit lacking the desired selectivity against NEP. Functionally, 27and 29 were the two most efficacious compounds from this study, producing sustained inhibition of ECE-1 activity in rats, as measured by their ability to block the hypertensive effects induced by big ET-1. This profile was similar to that of a potent ET(A)/ET(B) dual receptor antagonist, SB 209670. Due to their favorable in vitro and in vivo profiles, 27 (CGS 34043) and 29 (CGS 35066) constitute new pharmacological tools useful in assessing the role of ECE-1 in pathological conditions.

Economic and clinical impact of a pharmacy-based filgrastim protocol in oncology patients.

The effects of a clinical protocol for filgrastim use in oncology patients were studied. A chart review was conducted for every fourth oncology inpatient who received filgrastim at a community hospital between January and June 1996 to determine how filgrastim was being used in the hospital's oncology patients. The results were presented to the oncology committee, and a filgrastim protocol was implemented. The protocol stated that filgrastim would be discontinued when the absolute neutrophil count (ANC) was > or =1500 cells/mm3 for two days after the neutrophil nadir. Six months after the protocol was implemented, a follow-up evaluation was conducted by reviewing the chart for every fourth oncology patient who received filgrastim between November 1996 and April 1997. Twenty-one patient charts were reviewed before the protocol was implemented, and 34 charts were reviewed after implementation. The results showed there was compliance with the protocol for 19 (76%) of the 25 patients evaluable for compliance. Sixty-seven percent of patients were febrile before the protocol was implemented, and 56% were febrile afterward. Ten percent of patients had documented infections before implementation, compared with 12% afterward. The average ANC at which filgrastim was discontinued before and after the protocol was implemented was 6839 and 5538 cells/mm3, respectively. Filgrastim was discontinued by a pharmacist in 32% of cases. A $22,416 cost saving was achieved in the first six months after protocol implementation, with no compromise in clinical efficacy. A pharmacy-based protocol for discontinuing filgrastim therapy in oncology patients saved a community hospital more than $22,000 in the first six months withno adverse impact on the drug's effectiveness.

Level of ICAM-1 surface expression on virus producer cells influences both the amount of virion-bound host ICAM-1 and human immunodeficiency virus type 1 infectivity.

Using virions harvested from 293T cells stably expressing either low or high levels of surface ICAM-1, we determined that the number of virus-embedded host ICAM-1 proteins is positively influenced by the expression level of ICAM-1 on virus producer cells. Moreover, the increase in virion-bound host cell membrane ICAM-1 led to a concomitant enhancement of virus infectivity when a T-cell-tropic strain of human immunodeficiency virus type 1 (HIV-1) was used. The phenomenon was also seen when primary human cells were infected with virions pseudotyped with the envelope protein from a macrophage-tropic HIV-1 isolate, thus ruling out any envelope-specific effect. We also observed that target cells treated with NKI-L16, an anti-LFA-1 antibody known to increase the affinity of LFA-1 for ICAM-1, were markedly more susceptible to infection with HIV-1 particles bearing on their surfaces large numbers of host-derived ICAM-1 proteins. Given that cellular activation of leukocytes is known to modify the conformational state of LFA-1 and induce ICAM-1 surface expression, it is tempting to speculate that activation of virus-infected cells will lead to the production of HIV-1 particles bearing more host ICAM-1 on their surfaces and that such progeny virions will preferentially infect and replicate more efficiently in activated cells which are prevalent in lymphoid organs.

Exertional fatigue, sleep loss, and negative energy balance increase susceptibility to hypothermia.

The purpose of this study was to determine how chronic exertional fatigue and sleep deprivation coupled with negative energy balance affect thermoregulation during cold exposure. Eight men wearing only shorts and socks sat quietly during 4-h cold air exposure (10 degreesC) immediately after (<2 h, A) they completed 61 days of strenuous military training (energy expenditure approximately 4,150 kcal/day, energy intake approximately 3,300 kcal/day, sleep approximately 4 h/day) and again after short (48 h, SR) and long (109 days, LR) recovery. Body weight decreased 7.4 kg from before training to A, then increased 6.4 kg by SR, with an additional 6.4 kg increase by LR. Body fat averaged 12% during A and SR and increased to 21% during LR. Rectal temperature (Tre) was lower before and during cold air exposure for A than for SR and LR. Tre declined during cold exposure in A and SR but not LR. Mean weighted skin temperature (Tsk) during cold exposure was higher in A and SR than in LR. Metabolic rate increased during all cold exposures, but it was lower during A and LR than SR. The mean body temperature (0.67 Tre + 0.33 Tsk) threshold for increasing metabolism was lower during A than SR and LR. Thus chronic exertional fatigue and sleep loss, combined with underfeeding, reduced tissue insulation and blunted metabolic heat production, which compromised maintenance of body temperature. A short period of rest, sleep, and refeeding restored the thermogenic response to cold, but thermal balance in the cold remained compromised until after several weeks of recovery when tissue insulation had been restored.

Thermoregulatory responses to cold transients: effects of menstrual cycle in resting women.

Effects of the menstrual cycle on heat loss and heat production (M) and core and skin temperature responses to cold were studied in six unacclimatized female nonsmokers (18-29 yr of age). Each woman, resting supine, was exposed to a cold transient (ambient temperature = mean radiant temperature = 20 to -5 degrees C at -0.32 degrees C/min, relative humidity = 50 +/- 2%, wind speed = 1 m/s) in the follicular (F) phase (days 2-6) and midluteal (L) phase (days 19-23) of her menstrual cycle. Clothed in each of two ensembles with different thermal resistances, women performed multiple experiments in the F and L phases. Thermal resistance was 0.2 and 0.4 m2 . K . W-1 for ensembles A and B, respectively. Esophageal temperature (Tes), mean weighted skin temperature (Tsk), finger temperature (Tfing), and area-weighted heat flux were recorded continuously. Rate of heat debt (-S) and integrated mean body temperature (Tb,i) were calculated by partitional calorimetry throughout the cold ramp. Extensive peripheral vasoconstriction in the F phase during early periods of the ramp elevated Tes above thermoneutral levels. Shivering thermogenesis (DeltaM = M - Mbasal, W /m2) was highly correlated with declines in Tsk and Tfing (P <0.0001). There was a reduced slope in M as a function of Tb,i in the L phase with ensembles A (P < 0.02) and B (P < 0.01). Heat flux was higher and -S was less in the L phases with ensemble A (P < 0.05). An analytic model revealed that Tsk and Tes contribute as additive inputs and Tfing has a multiplicative effect on the total control of DeltaM during cold transients (R2 = 0.9). Endogenous hormonal levels at each menstrual cycle phase, core temperature and Tsk inputs, vascular responses, and variations in body heat balance must be considered in quantifying thermoregulatory responses in women during cold stress.

Response latencies for false memories: gist-based processes in normal aging.

Three experiments have demonstrated that age-related increases in both probability and speed of false recognitions for word lists depended on the use of a gist-based memory strategy. When test conditions promoted a gist strategy, both younger and older participants were as likely to falsely recognize a thematically associated lure as to correctly recognize a studied item, and both groups were equally fast in making these decisions. However, when test conditions deemphasized a gist-based strategy, older adults were more likely than younger adults, and faster, to falsely recognize both strong and weakly associated lures. These findings suggest an age-related increase in reliance on gist-based processing that may underlie age differences in false memory.

A qualitative study of Parent to Parent support for parents of children with special needs. Consortium to evaluate Parent to Parent.

OBJECTIVE: To examine qualitatively the experiences of parents participating in Parent to Parent programs. METHOD: Twenty-four parents of children with special needs, a subset of subjects in a larger quantitative study, participated in a semi-structured telephone interview to explore the impact and meaning of being matched with a trained supporting parent. RESULTS: Qualitative analysis reveals a successful match is contingent upon creation of a "reliable ally" in the supporting parent, comprised of four main components: (1) perceived sameness, (2) situational comparisons that enable learning and growth, (3) round-the-clock availability of support, and (4) mutuality of support. CONCLUSIONS: Parent to Parent support creates a community of similar others trained to listen and be supportive and provides an opportunity for matched parents to experience equality and mutuality in their relationship. Findings also identify the need for quality control in Parent to Parent programs and the importance of such programs as an adjunct to traditional professional services.