Humans and Water in Desert “Refugium” Areas: Palynological Evidence of Climate Oscillations and Cultural Developments in Early and Mid-Holocene Saharan Edges

Saharan anthropic deposits from archaeological sites, located along wadis or close to lakes, and sedimentary sequences from permanent and dried basins demonstrate that water has always been an attractive environmental feature, especially during periods of drought. This paper reports on two very different examples of Holocene sites where “humans and water” coexisted during dry periods, as observed by stratigraphic, archaeological and palynological evidence. Independent research was carried out on the Jefara Plain (Libya, 32°N) and the Gobero area (Niger, 17°N), at the extreme northern and southern limits of the Sahara, respectively. The histories of the Jefara and Gobero areas, as revealed by the archaeological and palaeoenvironmental reconstructions, suggest that these areas were likely to have been visited and exploited for a long time, acting as anthropic refugia, and therefore they have been profoundly transformed. Human presence and actions have conditioned the local growing of plants and selected a more or less synanthropic flora. Today, modern conservation strategies should take into consideration that water reservoirs, which are crucial for the long-term conservation of biodiversity, have provided refugia in the past just as they presently do under global warming conditions

Perioperative standard oral nutrition supplements versus immunonutrition in patients undergoing colorectal resection in an Enhanced Recovery (ERAS) protocol

To compare immunonutrition versus standard high calorie nutrition in patients undergoing elective colorectal resection within an Enhanced Recovery After Surgery (ERAS) program. Despite progress in recent years in the surgical management of patients with colorectal cancer (ERAS programs), postoperative complications are frequent. Nutritional supplements enriched with immunonutrients have recently been introduced into clinical practice. However, the extent to which the combination of ERAS protocols and immunonutrition benefits patients undergoing colorectal cancer surgery is unknown. The SONVI study is a prospective, multicenter, randomized trial with 2 parallel treatment groups receiving either the study product (an immune-enhancing feed) or the control supplement (a hypercaloric hypernitrogenous supplement) for 7 days before colorectal resection and 5 days postoperatively. A total of 264 patients were randomized. At baseline, both groups were comparable in regards to age, sex, surgical risk, comorbidity, and analytical and nutritional parameters. The median length of the postoperative hospital stay was 5 days with no differences between the groups. A decrease in the total number of complications was observed in the immunonutrition group compared with the control group, primarily due to a significant decrease in infectious complications (23.8% vs. 10.7%, P=0.0007). Of the infectious complications, wound infection differed significantly between the groups (16.4% vs. 5.7%, P=0.0008). Other infectious complications were lower in the immunonutrition group but were not statistically significantly different. The implementation of ERAS protocols including immunonutrient-enriched supplements reduces the complications of patients undergoing colorectal resection

Lakeside Cemeteries in the Sahara: 5000 Years of Holocene Population and Environmental Change

Background: Approximately two hundred human burials were discovered on the edge of a paleolake in Niger that providea uniquely preserved record of human occupation in the Sahara during the Holocene (,8000 B.C.E. to the present). CalledGobero, this suite of closely spaced sites chronicles the rapid pace of biosocial change in the southern Sahara in response tosevere climatic fluctuation.Methodology/Principal Findings: Two main occupational phases are identified that correspond with humid intervals in theearly and mid-Holocene, based on 78 direct AMS radiocarbon dates on human remains, fauna and artifacts, as well as 9 OSLdates on paleodune sand. The older occupants have craniofacial dimensions that demonstrate similarities with mid-Holocene occupants of the southern Sahara and Late Pleistocene to early Holocene inhabitants of the Maghreb. Theirhyperflexed burials compose the earliest cemetery in the Sahara dating to ,7500 B.C.E. These early occupants abandon thearea under arid conditions and, when humid conditions return ,4600 B.C.E., are replaced by a more gracile people withelaborated grave goods including animal bone and ivory ornaments.Conclusions/Significance: The principal significance of Gobero lies in its extraordinary human, faunal, and archaeologicalrecord, from which we conclude the following:(1) The early Holocene occupants at Gobero (7700–6200 B.C.E.) were largely sedentary hunter-fisher-gatherers withlakeside funerary sites that include the earliest recorded cemetery in the Sahara.(2) Principal components analysis of craniometric variables closely allies the early Holocene occupants at Gobero with askeletally robust, trans-Saharan assemblage of Late Pleistocene to mid-Holocene human populations from the Maghreband southern Sahara.(3) Gobero was abandoned during a period of severe aridification possibly as long as one millennium (6200–5200 B.C.E).(4) More gracile humans arrived in the mid-Holocene (5200–2500 B.C.E.) employing a diversified subsistence economybased on clams, fish, and savanna vertebrates as well as some cattle husbandry.(5) Population replacement after a harsh arid hiatus is the most likely explanation for the occupational sequence at Gobero.(6) We are just beginnin

MicroRNAs targeting oncogenes are down-regulated in pancreatic malignant transformation from benign tumors

BACKGROUND MicroRNA (miRNA) expression profiles have been described in pancreatic ductal adenocarcinoma (PDAC), but these have not been compared with pre-malignant pancreatic tumors. We wished to compare the miRNA expression signatures in pancreatic benign cystic tumors (BCT) of low and high malignant potential with PDAC, in order to identify miRNAs deregulated during PDAC development. The mechanistic consequences of miRNA dysregulation were further evaluated. METHODS Tissue samples were obtained at a tertiary pancreatic unit from individuals with BCT and PDAC. MiRNA profiling was performed using a custom microarray and results were validated using RT-qPCR prior to evaluation of miRNA targets. RESULTS Widespread miRNA down-regulation was observed in PDAC compared to low malignant potential BCT. We show that amongst those miRNAs down-regulated, miR-16, miR-126 and let-7d regulate known PDAC oncogenes (targeting BCL2, CRK and KRAS respectively). Notably, miR-126 also directly targets the KRAS transcript at a "seedless" binding site within its 3'UTR. In clinical specimens, miR-126 was strongly down-regulated in PDAC tissues, with an associated elevation in KRAS and CRK proteins. Furthermore, miR-21, a known oncogenic miRNA in pancreatic and other cancers, was not elevated in PDAC compared to serous microcystic adenoma (SMCA), but in both groups it was up-regulated compared to normal pancreas, implicating early up-regulation during malignant change. CONCLUSIONS Expression profiling revealed 21 miRNAs down-regulated in PDAC compared to SMCA, the most benign lesion that rarely progresses to invasive carcinoma. It appears that miR-21 up-regulation is an early event in the transformation from normal pancreatic tissue. MiRNA expression has the potential to distinguish PDAC from normal pancreas and BCT. Mechanistically the down-regulation of miR-16, miR-126 and let-7d promotes PDAC transformation by post-transcriptional up-regulation of crucial PDAC oncogenes. We show that miR-126 is able to directly target KRAS; re-expression has the potential as a therapeutic strategy against PDAC and other KRAS-driven cancers

O cultivo da macieira na Itália: porta-enxertos, cultivares, adubação e irrigação

A Itália é um dos principais países produtores de maçãs na Europa, destinada principalmente ao consumo in natura no mercado nacional e internacional. A produção e a qualidade dos frutos é dependente da cultivar, do porta-enxerto e das práticas de manejo, como a adubação e a irrigação adotado no pomar. Esta revisão tem por objetivo reportar as principais cultivares e porta-enxertos de macieira e o manejo da adubação e irrigação e suas atualizações em pomares de macieira da Itália. Os programas de melhoramento genético nesse país envolveram a seleção de cultivares e porta-enxertos de macieira que permitem a obtenção de altas produtividades e frutos de qualidade exigida pelo mercado consumidor. No manejo da adubação e irrigação, os nutrientes e a água têm sido fornecidos em quantidades próximas a real necessidade das plantas, proporcionando nutrição adequada, produção satisfatória e frutos de boa qualidade, além de evitar, sempre que possível, as perdas de nutrientes e água no ambiente

The Shaqadud Archaeological Project (Sudan): exploring prehistoric cultural adaptations in the Sahelian hinterlands

The authors present preliminary results from a new research project based in Jebel Shaqadud, Sudan. Their findings highlight the potential for this region's archaeological record to expand our understanding of the adaptation strategies used by human groups in arid north-east African environments away from rivers and lakes during the Holocene. Furthermore, they present exceptionally early radiocarbon dates that push postglacial human occupation in the eastern Sahel back to the twelfth millennium BP

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Cervical intraepithelial neoplasia disease progression is associated with increased vaginal microbiome diversity

Persistent infection with oncogenic Human Papillomavirus (HPV) is necessary for cervical carcinogenesis. Although evidence suggests that the vaginal microbiome plays a functional role in the persistence or regression of HPV infections, this has yet to be described in women with cervical intra-epithelial neoplasia (CIN). We hypothesised that increasing microbiome diversity is associated with increasing CIN severity. llumina MiSeq sequencing of 16S rRNA gene amplicons was used to characterise the vaginal microbiota of women with low-grade squamous intra-epithelial lesions (LSIL; n = 52), high-grade (HSIL; n = 92), invasive cervical cancer (ICC; n = 5) and healthy controls (n = 20). Hierarchical clustering analysis revealed an increased prevalence of microbiomes characterised by high-diversity and low levels of Lactobacillus spp. (community state type-CST IV) with increasing disease severity, irrespective of HPV status (Normal = 2/20,10%; LSIL = 11/52,21%; HSIL = 25/92,27%; ICC = 2/5,40%). Increasing disease severity was associated with decreasing relative abundance of Lactobacillus spp. The vaginal microbiome in HSIL was characterised by higher levels of Sneathia sanguinegens (P < 0.01), Anaerococcus tetradius (P < 0.05) and Peptostreptococcus anaerobius (P < 0.05) and lower levels of Lactobacillus jensenii (P < 0.01) compared to LSIL. Our results suggest advancing CIN disease severity is associated with increasing vaginal microbiota diversity and may be involved in regulating viral persistence and disease progression

Immunohistochemical analysis of changes in signaling pathway activation downstream of growth factor receptors in pancreatic duct cell carcinogenesis

<p>Abstract</p> <p>Background</p> <p>The pathogenesis of pancreatic ductal adenocarcinoma (PDAC) involves multi-stage development of molecular aberrations affecting signaling pathways that regulate cancer growth and progression. This study was performed to gain a better understanding of the abnormal signaling that occurs in PDAC compared with normal duct epithelia.</p> <p>Methods</p> <p>We performed immunohistochemistry on a tissue microarray of 26 PDAC, 13 normal appearing adjacent pancreatic ductal epithelia, and 12 normal non-PDAC ducts. We compared the levels of 18 signaling proteins including growth factor receptors, tumor suppressors and 13 of their putative downstream phosphorylated (p-) signal transducers in PDAC to those in normal ductal epithelia.</p> <p>Results</p> <p>The overall profiles of signaling protein expression levels, activation states and sub-cellular distribution in PDAC cells were distinguishable from non-neoplastic ductal epithelia. The ERK pathway activation was correlated with high levels of ^S2448p-mTOR (100%, p = 0.05), ^T389p-S6K (100%, p = 0.02 and ^S235/236p-S6 (86%, p = 0.005). Additionally, ^T389p-S6K correlated with ^S727p-STAT3 (86%, p = 0.005). Advanced tumors with lymph node metastasis were characterized by high levels of ^S276p-NFκB (100%, p = 0.05) and ^S9p-GSK3β (100%, p = 0.05). High levels of PKBβ/AKT2, EGFR, as well as nuclear ^T202/Y204p-ERK and ^T180/Y182p-p38 were observed in normal ducts adjacent to PDAC compared with non-cancerous pancreas.</p> <p>Conclusion</p> <p>Multiple signaling proteins are activated in pancreatic duct cell carcinogenesis including those associated with the ERK, PKB/AKT, mTOR and STAT3 pathways. The ERK pathway activation appears also increased in duct epithelia adjacent to carcinoma, suggesting tumor micro-environmental effects.</p