Frequent neck US in papillary thyroid cancer likely detects non-actionable findings.

BACKGROUND: American Thyroid Association (ATA) low-intermediate-risk papillary thyroid cancer (PTC) patients without structural and biochemical evidence of disease on initial post-treatment evaluation have a low risk of recurrence. Studies have shown that with current ultrasound scans (US) and thyroglobulin assays, recurrences mostly occurred 2-8 years after initial therapy. The ATA recommends that neck US be done 6-12 months after surgery to establish patient's response to therapy, then periodically depending on risk of recurrence. The lack of clarity in recommendations on timing of follow-up US and fear of recurrence leads to frequent tests. OBJECTIVES: To evaluate the utility of routine neck US in ATA low-intermediate-risk PTC patients with no structural disease on neck US and non-stimulated thyroglobulin <1.0 ng/mL after initial therapy. METHODS: A retrospective study of 93 patients from Singapore, Saudi Arabia and Argentina with ATA low (n = 49) to intermediate (n = 44) risk PTC was conducted between 1998 and 2017. The outcome was to measure the frequency of identifying structural disease recurrence and non-actionable US abnormalities. RESULTS: Over a median follow-up of 5 years, five of the 93 patients (5.4%) developed structural neck recurrence on US at a median of 2.5 years after initial treatment. Indeterminate US abnormalities were detected in 19 of the 93 patients (20.4%) leading to additional tests, which did not detect significant disease. CONCLUSION: In ATA low-intermediate-risk PTC with no suspicious findings on neck US and a non-stimulated thyroglobulin of <1.0 ng/mL after initial therapy, frequent US is more likely to identify non-actionable abnormalities than clinically significant disease.

Morbidly adherent placenta: One-year case series in a tertiary hospital.

OBJECTIVE: To analyse the clinical characteristics of patients with morbidly adherent placenta (MAP). Findings of this study will be used to identify patients at risk of MAP and to outline the best management strategy to deal with this devastating condition. METHODS: Delivery records in Hospital Sultanah Nur Zahirah, Terengganu from 1st. January 2016 until 31st. December 2016 were reviewed and analysed. RESULTS: Out of the 15,837 deliveries, eight cases of MAP were identified. Six out of eight patients had previous caesarean scar with concomitant placenta praevia, the other two patients had previous caesarean scar with history of placenta praevia in previous pregnancies. Seven out of eight cases were suspected to have MAP based on risk factors. Correct diagnosis was made by ultrasound in five patients, all with histologically confirmed moderate/severe degree of abnormal placentation. The other two cases of 'unlikely MAP', demonstrated segmental MAP intra-operatively with histologically confirmed milder degree of abnormal placentation. Total intraoperative blood loss ranged from 0.8 to 20 litres. Prophylactic internal iliac artery balloon occlusion was associated with significantly less blood loss. CONCLUSION: Antenatal diagnosis is essential in outlining the best management strategy in patients with MAP. Ultrasound may not be accurate in ruling out lower degree of MAP. Apart from having a scarred uterus with concomitant placenta praevia, history of having placenta praevia in previous pregnancy is also a risk factor for MAP. Prophylactic internal iliac artery balloon occlusion is associated with significantly less blood loss and should be considered in cases suspected with MAP.

Effects of prebiotic, protein level, and stocking density on performance, immunity, and stress indicators of broilers.

An experiment was conducted to determine the effects of period on the performance, immunity, and some stress indicators of broilers fed 2 levels of protein and stocked at a normal or high stocking density. Experimental treatments consisted of a 2 × 2 × 2 factorial arrangement with 2 levels of prebiotic (with or without prebiotic), 2 levels of dietary CP [NRC-recommended or low CP level (85% of NRC-recommended level)], and 2 levels of stocking density (10 birds/m(2) as the normal density or 16 birds/m(2) as the high density), for a total of 8 treatments. Each treatment had 5 replicates (cages). Birds were reared in 3-tiered battery cages with wire floors in an open-sided housing system under natural tropical conditions. Housing and general management practices were similar for all treatment groups. Starter and finisher diets in mash form were fed from 1 to 21 d and 22 to 42 d of age, respectively. Supplementation with a prebiotic had no significant effect on performance, immunity, and stress indicators (blood glucose, cholesterol, corticosterone, and heterophil:lymphocyte ratio). Protein level significantly influenced broiler performance but did not affect immunity or stress indicators (except for cholesterol level). The normal stocking density resulted in better FCR and also higher antibody titer against Newcastle disease compared with the high stocking density. However, density had no significant effect on blood levels of glucose, cholesterol, corticosterone, and the heterophil:lymphocyte ratio. Significant interactions between protein level and stocking density were observed for BW gain and final BW. The results indicated that, under the conditions of this experiment, dietary addition of a prebiotic had no significant effect on the performance, immunity, and stress indicators of broilers.

Effects of non-antibiotic feed additives on performance, tibial dyschondroplasia incidence and tibia characteristics of broilers fed low-calcium diets.

This experiment was conducted to investigate and compare the efficacy of different feed additives on performance, tibial dyschondroplasia (TD) incidence and tibia characteristics of male broilers fed low-calcium diets. A completely randomized design, with six treatments and five replicates of five chicks per each was used. Experimental treatments were: (i) Basal diet containing recommended level of calcium (0.9%) as control treatment (Ctrl), (ii) low-calcium (0.67%) diet without any additive (LC), (iii) low-calcium diet + probiotic (2 g/kg diet), (iv) low-calcium diet + prebiotic (2 g/kg diet), (v) low-calcium diet + synbiotic [mix of probiotic and prebiotic (each 2 g/kg diet)], (vi) low-calcium diet + organic acid (1.5 g/kg diet). Birds were reared in an open-sided house system under natural tropical condition until 21 days of age. Feeding with low-calcium diet negatively influenced broiler performance (body weight, body weight gain and feed conversion ratio) and tibia characteristics, whereas dietary inclusion of all feed additives had beneficial effects on above-mentioned parameters and helped the birds to overcome problems related to low-calcium diets. Different treatments had no effect on TD incidence.

Selected microbial groups and short-chain fatty acids profile in a simulated chicken cecum supplemented with two strains of Lactobacillus.

Among the bacterial fermentation end products in the chicken cecum, butyrate is of particular importance because of its nutritional properties for the epithelial cell and pathogen inhibitory effects in the gut. An in vitro experiment, operated with batch bioreactor, was conducted to quantify butyric-producing bacteria in a simulated broiler cecum supplemented with Lactobacillus salivarius ssp. salicinius JCM 1230 and Lactobacillus agilis JCM 1048 during 24 h of incubation. Selected bacterial species were determined by real-time PCR and short-chain fatty acids and lactate concentrations were monitored. The results showed that after 24 h of incubation, Lactobacillus supplementation significantly increased the number of lactobacilli, bifidobacteria and Faecalibacterium prausnitzii in medium containing cecal content and lactobacilli supplementation (Cc + L) compared with the control (Cc). Addition of lactobacilli did not alter Escherichia coli and Clostridium butyricum, whereas it significantly (P < 0.05) reduced Salmonella in treatment Cc + L compared with the Cc treatment. Propionate and butyrate formation were significantly (P < 0.05) increased in treatment Cc + L as compared with the Cc treatment. Lactate was only detected in treatment containing 2 Lactobacillus strains. After 24 h of incubation, acetate concentration significantly (P < 0.05) decreased in all treatments. It was suggested that lactate produced by Lactobacillus in the cecal content improved the growth of butyric producers such as F. prausnitzii, which significantly increased butyrate accumulation. Additionally, the results showed that butyrate and propionate inhibited Salmonella without influencing the E. coli profile.

Gastrointestinal tract morphological alteration by unpleasant physical treatment and modulating role of Lactobacillus in broilers.

1. An experiment was conducted to determine the effects of supposedly unpleasant physical treatment on broiler performance, small intestinal development and ameliorating role of probiotics. 2. The following treatments were applied from day one: (1) chicks exposed to normal human contact fed basal diet (control); (2) chicks were exposed to unpleasant physical treatment and fed basal diet (UPT-BD); and (3) chicks were exposed to unpleasant physical treatment and fed basal diet supplemented with Lactobacillus (UPT-BDL). Chicks were exposed to UPT from days 1 to 21. Different segments of gastrointestinal tract were sampled at 14, 28, 35 and 42 d of age. 3. Broilers of UPT-BD had lower feed consumption compared with control group at 7 d of age. Overall, UPT-BDL birds showed higher body weight gain (BWG) and better feed conversion ratio (FCR) over the course of the experiment. 4. Birds of UPT-BD had lower concentrations of lactic, propionic and butyric acids in the caecum as compared with other groups at 14 d of age. Acetic acid concentration was profoundly decreased in both UPT groups compared to the control. 5. Duodenal villus height of UPT-BD broilers showed a slight reduction compared to the control and UPT-BDL birds at 14 d of age. Afterwards until day 42, UPT-BDL birds showed the highest villus height among treatments in different parts of the small intestine. 6. The results suggested that, even though UPT did not have significant inhibitory effects on the development of the small intestine and broiler performance, it negatively affected bacterial metabolic end products in the caecum, which could be ameliorated by the addition of Lactobacillus.

In vitro fermentation of broiler cecal content: the role of lactobacilli and pH value on the composition of microbiota and end products fermentation.

AIM: To assess the probiotic effects of Lactobacillus agilis JCM 1048 and L. salivarius ssp. salicinius JCM 1230 and the pH on the cecal microflora of chicken and metabolic end products. METHODS AND RESULTS: An in vitro system, operated with batch bioreactor, was used for this assessment. Selected bacterial species were monitored at two pH values, over 24 h of batch culture incubation. The concentration of short chain fatty acids (SCFA) and lactate in the fermented material was also determined. The addition of L. agilis JCM 1048 and L. salivarius ssp. salicinius JCM 1230 into vessel 2 (Cc + P) increased the total anaerobes, lactobacilli and bifidobacteria after 24 h incubation. Moreover, lactobacilli supplementation decreased the total aerobes and streptococci, but it did not have any effects on coliforms. The supplementation of lactobacilli in vessel 2 (Cc + P) was found to significantly increase the production of lactate, propionate and butyrate. Furthermore, pH did not alter the formation of butyrate, whereas the production of acetate and propionate was significantly decreased at pH = 5.8. CONCLUSIONS: L. agilis JCM 1048 and L. salivarius ssp. salicinius JCM 1230, as probiotic bacteria, have the ability to re-establish proper microbial balance by the formation of lactate as well as propionate, and stimulate butyrate-producing bacteria to produce butyrate in the chicken cecum. SIGNIFICANCE AND IMPACT OF THE STUDY: This study was the first to report this under in vitro conditions, highlighting the probiotic roles of the two Lactobacillus strains in broiler cecal fermentation at different initial pH. These useful data can be helpful in improving the fermentation process in chicken cecum.

Structure-based design of novel HIV-1 protease inhibitors to combat drug resistance.

Structure-based design and synthesis of novel HIV protease inhibitors are described. The inhibitors are designed specifically to interact with the backbone of HIV protease active site to combat drug resistance. Inhibitor 3 has exhibited exceedingly potent enzyme inhibitory and antiviral potency. Furthermore, this inhibitor maintains impressive potency against a wide spectrum of HIV including a variety of multi-PI-resistant clinical strains. The inhibitors incorporated a stereochemically defined 5-hexahydrocyclopenta[b]furanyl urethane as the P2-ligand into the (R)-(hydroxyethylamino)sulfonamide isostere. Optically active (3aS,5R,6aR)-5-hydroxy-hexahydrocyclopenta[b]furan was prepared by an enzymatic asymmetrization of meso-diacetate with acetyl cholinesterase, radical cyclization, and Lewis acid-catalyzed anomeric reduction as the key steps. A protein-ligand X-ray crystal structure of inhibitor 3-bound HIV-1 protease (1.35 A resolution) revealed extensive interactions in the HIV protease active site including strong hydrogen bonding interactions with the backbone. This design strategy may lead to novel inhibitors that can combat drug resistance.

High resolution crystal structures of HIV-1 protease with a potent non-peptide inhibitor (UIC-94017) active against multi-drug-resistant clinical strains.

The compound UIC-94017 (TMC-114) is a second-generation HIV protease inhibitor with improved pharmacokinetics that is chemically related to the clinical inhibitor amprenavir. UIC-94017 is a broad-spectrum potent inhibitor active against HIV-1 clinical isolates with minimal cytotoxicity. We have determined the high-resolution crystal structures of UIC-94017 in complexes with wild-type HIV-1 protease (PR) and mutant proteases PR(V82A) and PR(I84V) that are common in drug-resistant HIV. The structures were refined at resolutions of 1.10-1.53A. The crystal structures of PR and PR(I84V) with UIC-94017 ternary complexes show that the inhibitor binds to the protease in two overlapping positions, while the PR(V82A) complex had one ordered inhibitor. In all three structures, UIC-94017 forms hydrogen bonds with the conserved main-chain atoms of Asp29 and Asp30 of the protease. These interactions are proposed to be critical for the potency of this compound against HIV isolates that are resistant to multiple protease inhibitors. Other small differences were observed in the interactions of the mutants with UIC-94017 as compared to PR. PR(V82A) showed differences in the position of the main-chain atoms of residue 82 compared to PR structure that better accommodated the inhibitor. Finally, the 1.10A resolution structure of PR(V82A) with UIC-94017 showed an unusual distribution of electron density for the catalytic aspartate residues, which is discussed in relation to the reaction mechanism.

Azithromycin versus doxycycline for genital chlamydial infections: a meta-analysis of randomized clinical trials.

BACKGROUND: Azithromycin and doxycycline are recommended for treatment of genital Chlamydia trachomatis infection. A systematic review comparing these antibiotics could affect treatment guidelines. GOAL: The goal was to perform a meta-analysis to evaluate the efficacy and tolerance of azithromycin versus doxycycline for genital chlamydial infection. STUDY DESIGN: Studies were identified by searching computerized English-language databases for the period 1975 to August 2001, supplemented by a manual bibliographic search. Criteria for inclusion were (1) randomized trial design; (2) regimens of oral doxycycline (100 mg twice daily for 7 days) and oral azithromycin (1 g once); (3) males >15 years of age and nonpregnant females >15 years of age; (4) and evaluation of microbial cure at follow-up. Data were extracted on diagnostic assay, follow-up time, study design, sponsorship, patients' characteristics, adverse events, attrition rates, and outcomes. RESULTS: Twelve trials met the inclusion criteria; 1543 patients were evaluated for microbial cure and 2171 for adverse events. Cure rates were 97% for azithromycin and 98% for doxycycline. Adverse events occurred in 25% and 23% of patients treated with azithromycin and doxycycline, respectively. After pooling of the data, differences in efficacy and risk were computed. The efficacy difference for microbial cure (0.01; 95% CI, -0.01-0.02) and the risk difference for adverse events (0.01; 95% CI, -0.02-0.04) between the two drugs were not statistically significant. CONCLUSION: Azithromycin and doxycycline are equally efficacious in achieving microbial cure and have similar tolerability. Further head-to-head trials comparing these antibiotics are unnecessary.