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The range of the mosquito Aedes aegypti continues to expand, putting more than two billion people at risk of arboviral infection. The sterile insect technique (SIT) has been used to successfully combat agricultural pests at large scale, but not mosquitoes, mainly because of challenges with consistent production and distribution of high-quality male mosquitoes. We describe automated processes to rear and release millions of competitive, sterile male Wolbachia-infected mosquitoes, and use of these males in a large-scale suppression trial in Fresno County, California. In 2018, we released 14.4 million males across three replicate neighborhoods encompassing 293 hectares. At peak mosquito season, the number of female mosquitoes was 95.5% lower (95% CI, 93.6–96.9) in release areas compared to non-release areas, with the most geographically isolated neighborhood reaching a 99% reduction. This work demonstrates the high efficacy of mosquito SIT in an area ninefold larger than in previous similar trials, supporting the potential of this approach in public health and nuisance-mosquito eradication programs.Mosquitoes are nearly eradicated in three suburbs of California using accurately sorted sterile male mosquitoes.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Antigen Ki-67 is a nuclear protein expressed in proliferating mammalian cells. It is widely used in cancer histopathology but its functions remain unclear. Here, we show that Ki-67 controls heterochromatin organisation. Altering Ki-67 expression levels did not significantly affect cell proliferation in vivo. Ki-67 mutant mice developed normally and cells lacking Ki-67 proliferated efficiently. Conversely, upregulation of Ki-67 expression in differentiated tissues did not prevent cell cycle arrest. Ki-67 interactors included proteins involved in nucleolar processes and chromatin regulators. Ki-67 depletion disrupted nucleologenesis but did not inhibit pre-rRNA processing. In contrast, it altered gene expression. Ki-67 silencing also had wide-ranging effects on chromatin organisation, disrupting heterochromatin compaction and long-range genomic interactions. Trimethylation of histone H3K9 and H4K20 was relocalised within the nucleus. Finally, overexpression of human or Xenopus Ki-67 induced ectopic heterochromatin formation. Altogether, our results suggest that Ki-67 expression in proliferating cells spatially organises heterochromatin, thereby controlling gene expression. Living cells divide in two to produce new cells. In mammals, cell division is strictly controlled so that only certain groups of cells in the body are actively dividing at any time. However, some cells may escape these controls so that they divide rapidly and form tumors. A protein called Ki-67 is only produced in actively dividing cells, where it is located in the nucleus – the structure that contains most of the cell’s DNA. Researchers often use Ki-67 as a marker to identify which cells are actively dividing in tissue samples from cancer patients, and previous studies indicated that Ki-67 is needed for cells to divide. However, the exact role of this protein was not clear. Before cells can divide they need to make large amounts of new proteins using molecular machines called ribosomes and it has been suggested that Ki-67 helps to produce ribosomes. Now, Sobecki et al. used genetic techniques to study the role of Ki-67 in mice. The experiments show that Ki-67 is not required for cells to divide in the laboratory or to make ribosomes. Instead, Ki-67 alters the way that DNA is packaged in the nucleus. Loss of Ki-67 from mice cells resulted in DNA becoming less compact, which in turn altered the activity of genes in those cells. Sobecki et al. also identified many other proteins that interact with Ki-67, so the next step following on from this research is to understand how Ki-67 alters DNA packaging at the molecular level. Another future challenge will be to find out if inhibiting the activity of Ki-67 can hinder the growth of cancer cells.

The esophagus is one of the most common target organs for both opportunistic infection and neoplasms in patient with HIV. Infectious (Candida and Herpes Simplex Virus) are the most common culprits. We report a patient with HIV who presented with recurrent episodes of dysphagia and odynophagia. Case: A 46-year-old woman with 8 year history of poorly controlled HIV presented with symptoms of odynophagia and inability to tolerate oral secretions. She was empirically treated with Valcyclovir and Diflucan for oral ulcers and esophageal candidiasis, respectively. Esophagogram showed deep penetration into the vocal cords without aspiration. Follow up Modified Barium Swallow was unremarkable. EGD showed a 5mm cratered mid esophageal ulcer without stigmata of bleeding which was biopsied. Stomach and duodenum were normal. Cytology along with smear, brushing and cultures were sent for fungal, viral and bacterial sources. Immuno-histochemical stains were negative for malignancy (Kaposi or lymphoma). Viral (HSV, CMV) markers, Groccott's Methenamine Silver (GMS) stain for fungus and PCP, and anaerobic culture were negative. Histology showed markedly inflamed squamous mucosa with ulceration covered by acute inflammatory exudate. Unfortunately, due to non-adherence to HAART therapy, patient continued to experience repeat episodes of dysphagia and odynophagia. Three follow up EGD with biopsy showed progressive increase in size of ulcer up to 20mm, along with negative infectious panel and worsening inflammation. Steroids were discussed as an option but not given due to worsening immunosuppressed state. Patient eventually required PEG tube for malnutrition without any change in ulceration due continued nonadherence to HAART therapy. Discussion: Idiopathic esophageal ulcers occur in about 10% patients with HIV either during acute retrovirus syndrome or in advanced HIV (CD4 < 50/uL) due to severe immunodeficiency. They tend to be located in middle esophagus; and present generally as a single ulcer, giant (5-10cm) in size, oval with profound depth. Exact pathophysiology is unknown and it is a diagnosis of exclusion requiring several negative biopsies which are negative for infectious process. Oral prednisone taper over 1 month with concurrent azole therapy is recommended. Conclusion: Characterization and identification of ulcers on endoscopy along with early steroid therapy and compliance with HAART therapy is key for treatment of HIV related esophageal ulcers.

Ethyl chloride is a common topical anesthetic. However, when abused as an inhalant, effects can range from headaches and dizziness to debilitating neurotoxicity requiring intubation. While previous case reports describe the short-term reversible neurotoxicity of ethyl chloride, ours show chronic morbidity and mortality outcome. During the initial evaluation, it is essential to consider the rising trend of commercially available inhalants being used as recreational drugs. We present a case of a middle-aged man presenting with subacute neurotoxicity due to repeated abuse of ethyl chloride.

Spontaneous isolated superior mesenteric artery dissection (SISMAD) is a rare potentially fatal disease. We present a case of cocaine-related SISMAD in a patient with abdominal pain. A 38-year-old African American male with hypertension and alcohol, cocaine, and tobacco abuse presented with abdominal pain and recent cocaine use. A CT angiogram revealed SISMAD; he was treated with conservative management. Cocaine and SISMAD share similar pathophysiologic mechanisms pertaining to vascular smooth muscle cell apoptosis and increased shear stress at fixed vascular positions. Our report emphasizes the need to consider cocaine abuse in SISMAD pathophysiology, risk stratification, and treatment algorithms in future studies.