Use of Integrated Malaria Management Reduces Malaria in Kenya

BACKGROUND: During an entomological survey in preparation for malaria control interventions in Mwea division, the number of malaria cases at the Kimbimbi sub-district hospital was in a steady decline. The underlying factors for this reduction were unknown and needed to be identified before any malaria intervention tools were deployed in the area. We therefore set out to investigate the potential factors that could have contributed to the decline of malaria cases in the hospital by analyzing the malaria control knowledge, attitudes and practices (KAP) that the residents in Mwea applied in an integrated fashion, also known as integrated malaria management (IMM). METHODS: Integrated Malaria Management was assessed among community members of Mwea division, central Kenya using KAP survey. The KAP study evaluated community members' malaria disease management practices at the home and hospitals, personal protection measures used at the household level and malaria transmission prevention methods relating to vector control. Concurrently, we also passively examined the prevalence of malaria parasite infection via outpatient admission records at the major referral hospital in the area. In addition we studied the mosquito vector population dynamics, the malaria sporozoite infection status and entomological inoculation rates (EIR) over an 8 month period in 6 villages to determine the risk of malaria transmission in the entire division. RESULTS: A total of 389 households in Mwea division were interviewed in the KAP study while 90 houses were surveyed in the entomological study. Ninety eight percent of the households knew about malaria disease while approximately 70% of households knew its symptoms and methods to manage it. Ninety seven percent of the interviewed households went to a health center for malaria diagnosis and treatment. Similarly a higher proportion (81%) used anti-malarial medicines bought from local pharmacies. Almost 90% of households reported owning and using an insecticide treated bed net and 81% reported buying the nets within the last 5 years. The community also used mosquito reduction measures including, in order of preference, environmental management (35%), mosquito repellent and smoke (31%) insecticide canister sprays (11%), and window and door screens (6%). These methods used by the community comprise an integrated malaria management (IMM) package. Over the last 4 years prior to this study, the malaria cases in the community hospital reduced from about 40% in 2000 to less than 10% by 2004 and by the year 2007 malaria cases decreased to zero. In addition, a one time cross-sectional malaria parasite survey detected no Plasmodium infection in 300 primary school children in the area. Mosquito vector populations were variable in the six villages but were generally lower in villages that did not engage in irrigation activities. The malaria risk as estimated by EIR remained low and varied by village and proximity to irrigation areas. The average EIR in the area was estimated at 0.011 infectious bites per person per day. CONCLUSIONS: The usage of a combination of malaria control tools in an integrated fashion by residents of Mwea division might have influenced the decreased malaria cases in the district hospital and in the school children. A vigorous campaign emphasizing IMM should be adopted and expanded in Mwea division and in other areas with different eco-epidemiological patterns of malaria transmission. With sustained implementation and support from community members integrated malaria management can reduce malaria significantly in affected communities in Africa

Modelling the Spatio-Temporal Cell Dynamics Reveals Novel Insights on Cell Differentiation and Proliferation in the Small Intestinal Crypt

We developed a slow structural relaxation model to describe cellular dynamics in the crypt of the mouse small intestine. Cells are arranged in a three dimensional spiral the size of which dynamically changes according to cell production demands of adjacent villi. Cell differentiation and proliferation is regulated through Wnt and Notch signals, the strength of which depends on the local cell composition. The highest level of Wnt activity is associated with maintaining equipotent stem cells (SC), Paneth cells and common goblet-Paneth cell progenitors (CGPCPs) intermingling at the crypt bottom. Low levels of Wnt signalling area are associated with stem cells giving rise to secretory cells (CGPCPs, enteroendocrine or Tuft cells) and proliferative absorptive progenitors. Deciding between these two fates, secretory and stem/absorptive cells, depends on Notch signalling. Our model predicts that Notch signalling inhibits secretory fate if more than 50% of cells they are in contact with belong to the secretory lineage. CGPCPs under high Wnt signalling will differentiate into Paneth cells while those migrating out from the crypt bottom differentiate into goblet cells. We have assumed that mature Paneth cells migrating upwards undergo anoikis. Structural relaxation explains the localisation of Paneth cells to the crypt bottom in the absence of active forces. The predicted crypt generation time from one SC is 4–5 days with 10–12 days needed to reach a structural steady state. Our predictions are consistent with experimental observations made under altered Wnt and Notch signalling. Mutations affecting stem cells located at the crypt floor have a 50% chance of being propagated throughout the crypt while mutations in cells above are rarely propagated. The predicted recovery time of an injured crypt losing half of its cells is approximately 2 days

Wnt signaling in triple-negative breast cancer

Wnt signaling regulates a variety of cellular processes, including cell fate, differentiation, proliferation and stem cell pluripotency. Aberrant Wnt signaling is a hallmark of many cancers. An aggressive subtype of breast cancer, known as triple-negative breast cancer (TNBC), demonstrates dysregulation in canonical and non-canonical Wnt signaling. In this review, we summarize regulators of canonical and non-canonical Wnt signaling, as well as Wnt signaling dysfunction that mediates the progression of TNBC. We review the complex molecular nature of TNBC and the emerging therapies that are currently under investigation for the treatment of this disease

Single cell RNA-seq reveals profound transcriptional similarity between Barrett's oesophagus and oesophageal submucosal glands

Barrett’s oesophagus is a precursor of oesophageal adenocarcinoma. In this common condition, squamous epithelium in the oesophagus is replaced by columnar epithelium in response to acid reflux. Barrett’s oesophagus is highly heterogeneous and its relationships to normal tissues are unclear. Here we investigate the cellular complexity of Barrett’s oesophagus and the upper gastrointestinal tract using RNA-sequencing of single cells from multiple biopsies from six patients with Barrett’s oesophagus and two patients without oesophageal pathology. We find that cell populations in Barrett’s oesophagus, marked by LEFTY1 and OLFM4, exhibit a profound transcriptional overlap with oesophageal submucosal gland cells, but not with gastric or duodenal cells. Additionally, SPINK4 and ITLN1 mark cells that precede morphologically identifiable goblet cells in colon and Barrett’s oesophagus, potentially aiding the identification of metaplasia. Our findings reveal striking transcriptional relationships between normal tissue populations and cells in a premalignant condition, with implications for clinical practice