Sulfonamide as amide isostere for fine-tuning the gelation properties of physical gels

(S)-2-Stearamidopentanedioic acid (C₁₈-Glu) is a known LMW gelator that forms supramolecular gels in a variety of solvents. In this work, we have carried out the isosteric substitution of the amide group by a sulfonamide moiety yielding the new isosteric gelator (S)-2-(octadecylsulfonamido)pentanedioic acid (Sulfo-Glu). The gelation ability and the key properties of the corresponding gels were compared in terms of gelation concentration, gel-to-sol transition temperature, mechanical properties, morphology, and gelation kinetics in several organic solvents and water. This comparison was also extended to (S)-2-(4-hexadecyl-1H-1,2,3-triazol-4-yl)pentanedioic acid (Click-Glu), which also constitutes an isostere of C₁₈-Glu. The stabilizing interactions were explored through computational calculations. In general, Sulfo-Glu enabled the formation of non-toxic gels at lower concentrations, faster, and with higher thermal-mechanical stabilities than those obtained with the other isosteres in most solvents. Furthermore, the amide-sulfonamide isosteric substitution also influenced the morphology of the gel networks as well as the release rate of an embedded antibiotic (vancomycin) leading to antibacterial activity in vitro against Staphylococcus aureus.

Amide–sulfonamide isosteric substitution in a low-molecular-weight gelator enables fine-tuning of its gelation ability and the properties of the corresponding supramolecular gels.     

How Long Is Antibiotic Therapy Necessary After Urgent Cholecystectomy for Acute Cholecystitis?

Objective

The objective of the study was to analyze surgical site infection (SSI) frequency with different duration antibiotic courses to establish the minimum necessary duration.

Methods

This is an observational study of prospective surveillance of 287 consecutive patients (mean age 67.8 years) operated on for acute cholecystitis of grade II severity in the first 72 h. Postoperative antibiotics had been withdrawn before diagnosis of any infection as an inclusion criterion. Patients were classified into three groups, according to therapy duration: group 1 (0–4 days, n?=?45, 15.7 %); group 2 (5–7 days, n?=?75, 26.1 %); and group 3 (>7 days, n?=?167, 58.2 %). A multivariable analysis of risk infection was performed.

Results

Overall SSI frequency in groups 1, 2, and 3 was 2.2, 10.7, and 9 %, respectively. Risk analysis showed an increase in both crude and adjusted relative risks of overall infection in group 2 (crude relative risk (RR): 4.80 (0.62–37.13); adjusted RR, 2.03 (0.20–20.91)) and in group 3 (crude RR, 4.04 (0.55–29.79); adjusted RR, 2.35 (0.28–20.05)) by comparison with group 1, although without statistical significance. As a result, treatment lasting 4 days or less was not associated with overall surgical site infection incidence higher than longer treatment.

Conclusion

Antibiotic treatment over 4 days after early cholecystectomy provides no advantage in decreasing surgical site infection incidence.     

Body image differences in guatemalan-american and white college women

Abstract

Although eating disturbances in Hispanic populations have been reported in the literature, body image attitudes have not yet been examined in this minority group. Utilizing several self-report measures, this study assessed differences in body image among 57 Guatemalan-American and white female college students. As predicted, Guatemalan women reported greater body satisfaction, were less driven toward thinness, and revealed more positive attitudes toward obesity. Body image disparagement in Guatemalan women was related to the degree of acculturation to the mainstream culture. Results are discussed in the context of cultural influences on attitudes toward body shape and size in minority groups.     

Assessment of in vivo fetal growth and placental vascular function in a novel intrauterine growth restriction model of progressive uterine artery occlusion in guinea pigs

Key points

• Intrauterine growth restriction (IUGR) is associated with short‐ and long‐term detrimental cardiometabolic effects.
• Mice and rats are commonly used to assess IUGR, but differences in placental and fetal developmental physiology relative to those in humans highlight the need for alternative small animal IUGR models.
• We developed a guinea pig IUGR model by gradual occlusion of uterine arteries by ameroid constrictor implantation. In this model, reduced uterine blood flow was associated with IUGR, allowing in vivo assessment of fetal growth trajectory and umbilico‐placental vascular function in conscious animals.
• The intervention induces placental vascular dysfunction and remodelling, as well as altered fetal abdominal growth resulting in an asymmetric IUGR and preserved brain growth.

Abstract

Intra‐uterine growth restriction (IUGR) is associated with short and long‐term metabolic and cardiovascular alterations. Mice and rats have been extensively used to study the effects of IUGR, but there are notable differences in fetal and placental physiology relative to those of humans that argue for alternative animal models. This study proposes that gradual occlusion of uterine arteries from mid‐gestation in pregnant guinea pigs produces a novel model to better assess human IUGR. Fetal biometry and in vivo placental vascular function were followed by sonography and Doppler of control pregnant guinea pigs and sows submitted to surgical placement of ameroid constrictors in both uterine arteries (IUGR) at mid‐gestation (35 days). The ameroid constrictors induced a reduction in the fetal abdominal circumference growth rate (0.205 cm day⁻¹) compared to control (0.241 cm day⁻¹, P < 0.001) without affecting biparietal diameter growth. Umbilical artery pulsatility and resistance indexes at 10 and 20 days after surgery were significantly higher in IUGR animals than controls (P < 0.01). These effects were associated with a decrease in the relative luminal area of placental chorionic arteries (21.3 ± 2.2% vs. 33.2 ± 2.7%, P < 0.01) in IUGR sows at near term. Uterine artery intervention reduced fetal (∼30%), placental (∼20%) and liver (∼50%) weights (P < 0.05), with an increased brain to liver ratio (P < 0.001) relative to the control group. These data demonstrate that the ameroid constrictor implantations in uterine arteries in pregnant guinea pigs lead to placental vascular dysfunction and altered fetal growth that induces asymmetric IUGR.