Biocatalysis and process integration in the synthesis of semi-synthetic antibiotics

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The Dynamics of Norovirus Outbreak Epidemics: Recent Insights

Noroviruses are a major cause of gastroenteritis outbreaks worldwide. Norovirus outbreaks frequently occur as epidemics which appear to be related to both genetic and environmental factors. This review considers recent progress in understanding these factors. The norovirus genome undergoes continuous change and this appears to be important in the persistence of the virus in the community. Studies on the common GII.4 genotype have shown that some norovirus outbreak epidemics involving this genotype are correlated with specific changes in the genome. In contrast to the growing understanding of the role of genetic factors in norovirus outbreak epidemics, the role of environmental factors is less well understood. Topics reviewed here include long term excretion of norovirus in some individuals, long term survivability of norovirus in the environment, the role of meteorological factors in the control of norovirus outbreaks and the possible zoonotic transmission of the virus

The Incidence of Norovirus-Associated Gastroenteritis Outbreaks in Victoria, Australia (2002–2007) and Their Relationship with Rainfall

The relationship between the incidence of norovirus-associated gastroenteritis outbreaks (NAGOs) in Victoria, Australia for the period 2002–2007 and rainfall was examined. Statistical analysis involving the correlation between time series indicated that there was a statistically significant (p < 0.05) correlation between monthly NAGO incidence and average monthly rainfall. There was a lag of an average of about three months between peak average rainfall and a NAGO epidemic. The findings thus indicate rainfall can influence NAGO incidence. In an era where there is concern about the potential effects of global warming on weather patterns, it should be borne in mind that future changes in NAGO incidence may reflect altered world weather patterns

Ileal transposition:A non-restrictive bariatric surgical procedure that reduces body fat and increases ingestion-related energy expenditure

Background: Ileal Transposition (IT) was developed as a model to study body weight reduction without the restrictive or malabsorptive aspects of other bariatric surgeries, but the exact mechanisms of the alterations in body weight after IT are not completely understood. Objective: To provide a detailed description of the surgical procedure of IT, and describe its effect on energy balance parameters. Methods: Adult male Lewis rats underwent either IT (IT+) or sham (IT-) surgery. Following surgery body weight and energy intake were monitored. After attaining weight stability (> 30 days), energy expenditure and its components were assessed using indirect calorimetry at a day of fasting, limited intake, and ad libitum intake. At the end of the study body composition analysis was performed. Results: IT+ resulted in transiently reduced energy intake, increased ingestion-related energy expenditure (IEE) and decreased body and adipose tissue weight when compared to IT-. At weight stability, neither energy budget (i.e., energy intake - energy expenditure), nor energy efficiency was different in IT+ rats compared to IT-. Conclusion: Our data show that the primary cause of weight reduction following IT+ is a transient reduction in energy intake. If the increased IEE is related to a higher level of satiety, compensatory feeding to bridge body weight difference between IT+ and IT- rats is less likely to occur

Intestinal Oxygenation and Survival After Surgery for Necrotizing Enterocolitis:An Observational Cohort Study

OBJECTIVE: To assess whether regional intestinal oxygen saturation (rintSO2) and regional cerebral oxygen saturation (rcSO2) measurements aid in estimating survival of preterm infants after surgery for NEC. SUMMARY OF BACKGROUND DATA: Predicting survival after surgery for NEC is difficult yet of the utmost importance for counseling parents. METHODS: We retrospectively studied prospectively collected data of preterm infants with surgical NEC who had available rintSO2 and rcSO2 values measured via near-infrared spectroscopy 0-24 hours preoperatively. We calculated mean rintSO2 and rcSO2 for 60-120 minutes for each infant. We analyzed whether preoperative rintSO2 and rcSO2 differed between survivors and non-survivors, determined cut-off points, and assessed the added value to clinical variables. RESULTS: We included 22 infants, median gestational age 26.9 weeks [interquartile range (IQR): 26.3-28.4], median birth weight 1088 g [IQR: 730-1178]. Eleven infants died postoperatively. Preoperative rintSO2, but not rcSO2, was higher in survivors than in non-survivors [median: 63% (IQR: 42-68) vs 29% (IQR: 21-43), P 53% survived, whereas all infants with rintSO2 <35% died. Median C-reactive protein [138 mg/L (IQR: 83-179) vs 73 mg/L (IQR: 12-98), P < 0.01), lactate [1.1 mmol/L (IQR: 1.0-1.6) vs 4.6 mmol/L (IQR: 2.8-8.0), P < 0.01], and fraction of inspired oxygen [25% (IQR: 21-31) vs 42% (IQR: 30-80), P < 0.01] differed between survivors and non-survivors. Only rintSO2 remained significant in the multiple regression model. CONCLUSIONS: Measuring rintSO2, but not rcSO2, seems of added value to clinical variables in estimating survival of preterm infants after surgery for NEC. This may help clinicians in deciding whether surgery is feasible and to better counsel parents about their infants' chances of survival

Necrotizing Enterocolitis Associated with Congenital Heart Disease:a Different Entity?

Background: Necrotizing enterocolitis (NEC) predominantly occurs in preterm infants (PT-NEC). In term neonates, NEC occurs more frequently when a congenital heart disease is present (CHDNEC). Our aim was to evaluate differences and similarities in disease characteristics of PT-NEC versus CHD-NEC.Methods: In this retrospective case-control study we identified all CHD infants who developed NEC Bell's stage &gt;= 2 in our center from 2004 to 2014. We randomly selected (1:2 ratio) PT-NEC infants from the same period. Biochemical and clinical variables were retrieved from patient files.Results: We found 18 CHD-NEC infants and selected 36 PT-NEC infants (gestational age 28.3 [25-35.6] weeks vs. 38.6 [31.7-40.7] weeks). Postnatal age at onset was significantly lower in CHD-NEC patients (4 [2-24] vs. 11 [4-41] days, p &lt;0.001). Lowest pH levels were lower (7.21 [7.01-7.47] vs. 7.27 [6.68-7.39], p = 0.02), and highest CRP levels were higher (112.5 mg/L [5.0-425.0] vs. 66.0 [52-189.0], p = 0.05) in PT-NEC vs. CHD-NEC. Anatomic localisation of the disease differed: the colon was significantly more often involved in CHD-NEC versus PT-NEC (86% vs. 33%, p = 0.03). Mortality caused by NEC was not different (22% vs. 11%, p = 0.47).Conclusion: While outcome of NEC in both groups is similar, the predominant NEC localisation differed between CHD-NEC and PT-NEC patients. This suggests that both variants of the disease have a different underlying pathophysiological mechanism that predisposes different intestinal regions to develop NEC.Type of Study: Retrospective Case-Control Study. (C) 2018 Elsevier Inc. All rights reserved.</p

A critical role of hepatic GABA in the metabolic dysfunction and hyperphagia of obesity

Hepatic lipid accumulation is a hallmark of type II diabetes (T2D) associated with hyperinsulinemia, insulin resistance, and hyperphagia. Hepatic synthesis of GABA, catalyzed by GABA-transaminase (GABA-T), is upregulated in obese mice. To assess the role of hepatic GABA production in obesity-induced metabolic and energy dysregulation, we treated mice with two pharmacologic GABA-T inhibitors and knocked down hepatic GABA-T expression using an antisense oligonucleotide. Hepatic GABA-T inhibition and knockdown decreased basal hyperinsulinemia and hyperglycemia and improved glucose intolerance. GABA-T knockdown improved insulin sensitivity assessed by hyperinsulinemic-euglycemic clamps in obese mice. Hepatic GABA-T knockdown also decreased food intake and induced weight loss without altering energy expenditure in obese mice. Data from people with obesity support the notion that hepatic GABA production and transport are associated with serum insulin, homeostatic model assessment for insulin resistance (HOMA-IR), T2D, and BMI. These results support a key role for hepatocyte GABA production in the dysfunctional glucoregulation and feeding behavior associated with obesity

Gut Microbiota Composition of Biliary Atresia Patients Before Kasai Portoenterostomy Associates With Long-term Outcome

BACKGROUND AND AIMS: Biliary atresia (BA) is a cholestatic, fibro-obliterative cholangiopathy of unknown etiology. BA is primarily treated by a surgical approach, i.e. the Kasai portoenterostomy (KPE), to obtain clearance of jaundice (COJ). The gut microbiota (GM) composition has been associated with the course of several cholestatic liver diseases. It is largely unknown, however, whether GM composition associates with the outcome of KPE. We compared the GM composition of BA patients and controls and assessed if GM composition before KPE was related to COJ after KPE. METHODS: We compared feces of term born BA patients before KPE and controls (patients undergoing inguinal hernia repair) by 16S rRNA sequencing. Composition and alpha diversity of the GM were compared between BA and controls before KPE and after KPE, between patients with COJ vs. without COJ (total serum bilirubin < or ≥ 20 μmol/L < 6mo post-KPE). RESULTS: Alpha diversity was comparable between BA (n = 12, age 1.6[1.3-1.8]mo) and controls (n = 6, age 2.0[1.4-2.1]mo; P = 0.22). Compared to controls, BA patients had lower abundances of Bifidobacteriaceae (β=-1.98, P < 0.001) and Lachnospiraceae (β=-1.84, P = 0.007), and higher abundances of Streptococcus (β=1.13, P = 0.003). The alpha diversity prior to KPE correlated negatively with COJ (R = -0.63, P = 0.03). Lower alpha diversity pre-KPE was associated with COJ [+] (βlogit = -0.64, P = 0.04). We observed greater abundances of genus Acinetobacter (β=1.27, P = 0.03) and family Clostridiaceae (β=1.45, P = 0.03) and lower abundances of the family Enterobacteriaceae, (genera Klebsiella (β=-1.21, P = 0.01), Salmonella (β=-1.57, P = 0.02)) in COJ [+] vs. COJ [-]. CONCLUSIONS: The gut microbiota of biliary atresia patients prior to Kasai portoenterostomy associates with outcome, clearance of jaundice, suggestive of predictive and mechanistic roles of the gut microbiota composition in bile homeostasis

Analysis of urinary oligosaccharides in lysosomal storage disorders by capillary high-performance anion-exchange chromatography–mass spectrometry

Many lysosomal storage diseases are characterized by an increased urinary excretion of glycoconjugates and oligosaccharides that are characteristic for the underlying enzymatic defect. Here, we have used capillary high-performance anion-exchange chromatography (HPAEC) hyphenated to mass spectrometry to analyze free oligosaccharides from urine samples of patients suffering from the lysosomal storage disorders fucosidosis, α-mannosidosis, GM1-gangliosidosis, GM2-gangliosidosis, and sialidosis. Glycan fingerprints were registered, and the patterns of accumulated oligosaccharides were found to reflect the specific blockages of the catabolic pathway. Our analytical approach allowed structural analysis of the excreted oligosaccharides and revealed several previously unpublished oligosaccharides. In conclusion, using online coupling of HPAEC with mass spectrometric detection, our study provides characteristic urinary oligosaccharide fingerprints with diagnostic potential for lysosomal storage disorders

Topical vitamin A treatment of recalcitrant common warts

<p>Abstract</p> <p>Background</p> <p>Common warts (<it>verruca vulgaris</it>) are benign epithelial proliferations associated with human papillomavirus (HPV) infection. Salicylic acid and cryotherapy are the most frequent treatments for common warts, but can be painful and cause scarring, and have high failure and recrudescence rates. Topical vitamin A has been shown to be a successful treatment of common warts in prior informal studies.</p> <p>Case</p> <p>The subject is a healthy, physically-active 30 old female with a 9 year history of common warts on the back of the right hand. The warts resisted treatment with salicylic acid, apple cider vinegar and an over-the-counter blend of essential oils marketed for the treatment of warts. Daily topical application of natural vitamin A derived from fish liver oil (25,000 IU) led to replacement of all the warts with normal skin. Most of the smaller warts had been replaced by 70 days. A large wart on the middle knuckle required 6 months of vitamin A treatment to resolve completely.</p> <p>Conclusion</p> <p>Retinoids should be further investigated in controlled studies to determine their effectiveness in treating common warts and the broad range of other benign and cancerous lesions induced by HPVs.</p