Born of frustration: Using the frustrated Lewis pairs TMP-metal and BF3 ⋅OEt2 allows the regioselective metalation of pharmaceutically relevant diazines, such as pyrimidines, purines, and pyrazines. These metalations are often complementary to prior deprotonations performed without BF3 ⋅OEt2 . Especially attractive is a new sequential regioselective full functionalization of the pyrazine scaffold with a bulky (TMS)2 CH substituent.

BACKGROUND:

Urinary tract infections (UTIs) are common after kidney transplantation, with limited data to guide antibiotic prophylaxis.

METHODS:

Retrospective single-center study comparing sulfamethoxazole-trimethoprim 800/160 mg (SMZ/TMP) daily for 30 days followed by Monday, Wednesday, Friday for an additional 5 months (Group 1) versus SMZ/TMP Monday, Wednesday, Friday for 6 months plus ciprofloxacin 250 mg twice daily for 30 days (Group 2) on UTI incidence after kidney transplantation.

RESULTS:

There were 106 and 130 patients in Groups 1 and 2, respectively. Demographics and transplant characteristics were well matched, except for more patients in Group 2 on corticosteroid maintenance. At 1 year, more patients in Group 1 developed UTIs (23.6% vs. 10.8%; P=0.01) and the mean time to first UTI was shorter (96.6±79.5 vs. 168±89.7 days; P=0.01). UTIs caused by Enterococcus species were higher in Group 2 (28.6% vs. 4%; P=0.047) with enteric gram-negative bacilli accounting for the remaining infections. There was a similar incidence of enteric gram-negative antibiotic resistance to SMZ/TMP (75% vs. 80%; P=1.00) and ciprofloxacin (16.7% vs. 30%; P=0.39) in Groups 1 and 2. For Groups 1 and 2, the proportion of first UTIs requiring hospitalization was 48.9% vs. 40.6%, respectively (P=0.62). Female gender was a UTI risk factor (hazard ratio, 3.5; 95% confidence interval, 1.78-6.8; P=0.0003).

CONCLUSIONS:

The addition of a 30-day course of ciprofloxacin lowered the incidence of UTI; randomized prospective studies are needed to confirm the safety and efficacy of this approach.

Lipoproteins of temperate phage are a broad family of membrane proteins encoded in the lysogeny module of temperate phages. Expression of the ltpTP-J34 gene of temperate Streptococcus thermophilus phage TP-J34 interferes with phage infection at the stage of triggering DNA release and injection into the cell. Here, we report the first structure of a superinfection exclusion protein. We have expressed and determined the X-ray structure of LtpTP-J34 . The soluble domain of LtpTP-J34 is composed of a tandem of three-helix helix-turn-helix (HTH) domains exhibiting a highly negatively charged surface. By isolating mutants of lactococcal phage P008wt with reduced sensitivities to LtpTP-J34 and by genome sequencing of such mutants we obtained evidence supporting the notion that LtpTP-J34 targets the phage's tape measure protein (TMP) and blocks its insertion into the cytoplasmic membrane.

{[Fe(i)Pc(-2)(-)]·(TMP(+))}·0.5C6H14 () and {Co(i)Pc(-2)(-)}·(TMP(+)) () salts containing iron(i) and cobalt(i) phthalocyanine anions and N,N,N'-trimethylpiperazinium cations (TMP(+)) have been obtained as single crystals. The TMP(+) cations coordinate to the iron(i) centers in by free nitrogen atoms to form a weak N(TMP(+))-Fe bond of 2.568(3) and 2.553(3) Å length at 150 and 105 K, respectively. This is the first zwitterionic assembly containing anions and cations in one neutral coordination {[Fe(i)Pc(-2)(-)]·(TMP(+))} unit. The Fe(i)Pc(-2)(-) anions manifest strongly asymmetric EPR signals in the spectrum of which can be fitted well by four components at 298 K with g1 = 2.1770, g2 = 2.1681, g3 = 2.1425 and g4 = 2.0708. The signal is attributed to the low-spin (S = 1/2) Fe(i) with the d(7) configuration. The EPR spectrum of does not change qualitatively upon slow cooling from 298 down to 4 K. Quenching of the sample for seconds produces a different EPR spectrum at 4 K. This spectrum can be attributed to the frozen metastable state of Fe(i)Pc(-2)(-) which exists only at low temperatures and transfers to the spectrum observed for the slowly cooled sample above 70 K. Salt contains EPR silent cobalt(i) with the d(8) configuration and in this case the TMP(+) cations do not coordinate to the cobalt(i) atoms.

Empiric antibiotic usage is very common in clinical practice and Trimethoprim-Sulfamethoxazole (TMP-SMX) is one such antibiotic used extensively in primary care practice. Some patients experience serious adverse effects to the antibiotics that markedly increase the morbidity and the cost of medical care. We describe one such patient, a previously healthy 40-year-old Hispanic female who developed myositis and rhabdomyolysis secondary to TMP-SMX. To the best of our knowledge, this is the first report of TMP-SMX-induced rhabdomyolysis in an immunocompetent host.

Understanding how cooperative interactions evolve and persist remains a central challenge in biology. Many mutualisms are thought to be maintained by "partner fidelity feedback," in which each partner bases their investment on the benefits they receive. Yet, we know little about how benefits change as mutualists vary their investment, which is critical to understanding the balance between mutualism and antagonism in any given partnership. Using an obligate ant-plant mutualism, we manipulated the density of symbiotic acacia ants (Crematogaster mimosae) and examined how the costs and benefits to Acacia drepanolobium trees scaled with ant abundance. Benefits of ants to plants saturated with increasing ant abundance for protection from branch browsing by elephants and attack by branch galling midges, while varying linearly for protection from cerambycid beetles. In addition, the risk of catastrophic whole-tree herbivory by elephants was highest for trees with very low ant abundance. However, there was no relationship between ant abundance and herbivory by leaf-feeding invertebrates, nor by vertebrate browsers such as giraffe, steinbuck, and Grant's gazelle. Ant abundance did not significantly influence rates of branch growth on acacias, but there was a significant negative relationship between ant abundance and the number of fruits produced by host plants, suggesting that maintaining high-density ant colonies is costly. Because benefits to plants largely saturated with increasing colony size, while costs to plant reproduction increased, we suggest that ant colonies may achieve abundances that are higher than optimal for host plants. Our results highlight the conflicts of interest inherent in many mutualisms, and demonstrate the value of examining the shape of curves relating costs and benefits within these globally important interactions.

Infant laboratory abnormalities have been associated with exposure to antiretrovirals and to trimethoprim/sulfamethoxazole (TMP/SMX).We analyzed data from International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) Protocol P1025, a prospective cohort study of human immunodeficiency virus type 1 (HIV)-infected women and their infants. Live-born, singleton, HIV-uninfected infants with at least 6 months of follow-up who represented the first pregnancy on study of HIV-infected mothers with at least 1 prenatal visit, CD4 count, and viral load during pregnancy and who used at least 1 antiretroviral during pregnancy were eligible for inclusion in this analysis.The study population comprised 1524 infants. During the first 6 months of life, 7.4% of laboratory serious adverse events (SAEs) were related to glucose, 7.2% were related to hemoglobin, 8.7% were related to absolute neutrophil count, and 4.0% were related to total lymphocyte count. The likelihood of laboratory SAEs decreased with increasing age for hemoglobin, absolute neutrophil count, and glucose. Infant preterm birth and current receipt of antiretroviral(s) were the factors with the strongest associations with laboratory SAEs.The overall frequency of laboratory SAEs was low and decreased with age. Preterm infants are at higher risk of hemoglobin- and total lymphocyte count-related SAEs.

Aqueous solutions of four pharmaceutical compounds, belonging to the group of emergent contaminants of water: atenolol (ATL), hydrochlorothiazide (HCT), ofloxacin (OFX) and trimethoprim (TMP), have been treated with different oxidation systems, mainly, photocatalytic oxidation, ozonation and photocatalytic ozonation. TiO2 has been used as semiconductor for photocatalytic reactions both in the presence of air, oxygen or ozone-oxygen gas mixtures. Black light lamps mainly emitting at 365 nm were the source of radiation. In all cases, the influence of some variables (concentrations of semiconductor, ozone gas and pharmaceuticals and pH) on the removal of pharmaceuticals, total polyphenol content (TPC) and total organic carbon (TOC) was investigated. A discussion on the possible routes of pharmaceutical and intermediates (as TPC and TOC) elimination has been developed. Thus, OFX TiO2/UVA degradation mechanism seems to develop through the participation of non-hydroxyl free radical species. Furthermore, the presence of OFX inhibits the formation of hydroxyl radicals in the photocatalytic process. The most effective processes were those involving ozone that lead to complete disappearance of parent compounds in less than 30 min for initial pharmaceutical concentrations lower than 2.5 mg L(-1). In the ozonation systems, regardless of the pH and the presence of TiO2, pharmaceuticals are degraded through their direct reaction with ozone. Photocatalytic ozonation was the most efficient process for TPC and TOC removals (≥ 80% and ≥60% elimination after 2 h of treatment, respectively) as well as in terms of the ozone consumption efficiency (1, 5.5 and 4 mol of ozone consumed per mol of TOC mineralized, at pH 4, 7 and 9, respectively). Weakly acid conditions (pH 4) resulted to be the most convenient ones for TPC and TOC removal by photocatalytic ozonation. This was likely due to formation of hydroxyl radicals through the ozonide generated at these conditions.

Headspace gas composition and bicarbonate concentrations in media can affect methane production and other characteristics of rumen fermentation in in vitro gas production systems, but these 2 important factors have not been evaluated systematically. In this study, these 2 factors were investigated with respect to gas and methane production, in vitro digestibility of feed substrate, and volatile fatty acid (VFA) profile using in vitro gas production techniques. Three headspace gas compositions (N2 + CO2 + H2 in the ratio of 90:5:5, CO2, and N2) with 2 substrate types (alfalfa hay only, and alfalfa hay and a concentrate mixture in a 50:50 ratio) in a 3 × 2 factorial design (experiment 1) and 3 headspace compositions (N2, N2 + CO2 in a 50:50 ratio, and CO2) with 3 bicarbonate concentrations (80, 100, and 120 mM) in a 3 × 3 factorial design (experiment 2) were evaluated. In experiment 1, total gas production (TGP) and net gas production (NGP) was the lowest for CO2, followed by N2, and then the gas mixture. Methane concentration in headspace gas after fermentation was greater for CO2 than for N2 and the gas mixture, whereas total methane production (TMP) and net methane production (NMP) were the greatest for CO2, followed by the gas mixture, and then N2. Headspace composition did not affect in vitro digestibility or the VFA profile, except molar percentages of propionate, which were greater for CO2 and N2 than for the gas mixture. Methane concentration in headspace gas, TGP, and NGP were affected by the interaction of headspace gas composition and substrate type. In experiment 2, increasing concentrations of CO2 in the headspace decreased TGP and NGP quadratically, but increased the concentrations of methane, NMP, and in vitro fiber digestibility linearly, and TMP quadratically. Fiber digestibility, TGP, and NGP increased linearly with increasing bicarbonate concentrations in the medium. Concentrations of methane and NMP were unaffected by bicarbonate concentration, but TMP tended to increase due to increasing bicarbonate concentration. Although total VFA concentration and molar percentage of butyrate were unchanged, the molar percentage of acetate, and acetate-to-propionate ratio decreased, whereas the molar percentage of propionate increased quadratically with increasing bicarbonate concentration. This study demonstrated for the first time that headspace composition, especially CO2 content, and bicarbonate concentration in media could significantly influence gas and methane production, and rumen fermentation in gas production techniques.

  Japanese patients with normal renal function were retrospectively analyzed to characterize increases in serum creatinine (SCr) observed following the use of a sulfamethoxazole-trimethoprim (SMX-TMP) combination product and identify factors affecting these increases. In the patients studied (n=49), an individual comparison was conducted for the three factors of age group [≤74 years (n=21) vs. ≥75 years (n=28)], sex [male (n=24) vs. female (n=25)], and total dose throughout the treatment period [≤7 g (n=24) vs. ≥8 g (n=25)] to determine the extent of SCr increase following SMX-TMP combination product use. SCr increased significantly following SMX-TMP combination product use in patients ≤74 years of age and ≥75 years of age, in both males and females, and in patients with a total dose of ≥8 g (8 to 96 g) (p<0.05). Multivariate logistic regression analysis was used to determine the independence of these factors. Total dose was identified as an independent factor and had an odds ratio of 6.571 [95% confidence interval=1.735-24.882, p=0.006]. Post-treatment percent increases in SCr were compared using pre-treatment levels as the baseline. The group with a total dose of ≥8 g (mean 29.8 g) had a significant SCr increase of 18.4% (p=0.002), while the increase in the ≤7 g (mean 5.3 g) group was only 4.5%. The data showed that SCr increased by about 20% when the total dose taken over the treatment period was around 30 g (about 2.4 g as TMP) and indicated that total dose contributes more than age and sex to the post-treatment increase in SCr.