An exploratory pilot study on the involvement of APOE,HFE, C9ORF72 variants and comorbidities in neurocognitive and physical performance in a group of HIV-infected people

Metabolic Brain Disease - Cognitive decline of aging is modulated by chronic inflammation and comorbidities. In people with HIV-infection (PWH) it may also be affected by HIV-induced inflammation,...     

Analysis of three μ1‐AP1 subunits during zebrafish development

Background : The family of AP‐1 complexes mediates protein sorting in the late secretory pathway and it is essential for the development of mammals. The ubiquitously expressed AP‐1A complex consists of four adaptins γ1, β1, μ1A, and σ1A. AP‐1A mediates protein transport between the trans‐Golgi network and early endosomes. The polarized epithelia AP‐1B complex contains the μ1B‐adaptin. AP‐1B mediates specific transport of proteins from basolateral recycling endosomes to the basolateral plasma membrane of polarized epithelial cells. Results: Analysis of the zebrafish genome revealed the existence of three μ1‐adaptin genes, encoding μ1A, μ1B, and the novel isoform μ1C, which is not found in mammals. μ1C shows 80% sequence identity with μ1A and μ1B. The μ1C expression pattern largely overlaps with that of μ1A, while μ1B is expressed in epithelial cells. By knocking‐down the synthesis of μ1A, μ1B and μ1C with antisense morpholino techniques we demonstrate that each of these μ1 adaptins is essential for zebrafish development, with μ1A and μ1C being involved in central nervous system development and μ1B in kidney, gut and liver formation. Conclusions : Zebrafish is unique in expressing three AP‐1 complexes: AP‐1A, AP‐1B, and AP‐1C. Our results demonstrate that they are not redundant and that each of them has specific functions, which cannot be fulfilled by one of the other isoforms. Each of the μ1 adaptins appears to mediate specific molecular mechanisms essential for early developmental processes, which depends on specific intracellular vesicular protein sorting pathways. Developmental Dynamics 243:299–314, 2014. © 2013 Wiley Periodicals, Inc.     

Pathological response on surgical samples is an independent prognostic variable for patients with Stage Ib2–IIb cervical cancer treated with neoadjuvant chemotherapy and radical hysterectomy: An Italian multicenter retrospective study (CTF Study)

Objectives

The purpose of this retrospective multicenter study was to correlate patterns of recurrences and clinical outcome of cervical cancer patients who underwent neoadjuvant chemotherapy [NACT] to surgery.

Methods

This study was conducted on 333 patients with FIGO stage Ib2–IIb cervical cancer who underwent NACT to surgery with pelvic lymphadenectomy. The median follow-up was 66.5 months (range, 8–212 months). Overall optimal response rate was the sum of complete and optimal partial response rates.

Results

An overall optimal response was obtained in 64 patients (19.2%). As for the 220 sub-optimal responders (66.1%), 127 patients had negative nodes and negative parametria and/or surgical margins, 75 patients had positive nodes with positive or negative parametria and/or surgical margins, and 18 patients had positive parametria and/or surgical margins with negative nodes. At the time of the present analysis, 79 (23.7%) of the 333 patients had a recurrence after a median time of 14.9 months (range, 4.5–123 months). Recurrent disease was pelvic in 50 (63.3%), extra-pelvic in 22 (27.9%), and both in 7 (8.8%). On multivariate analysis, pathological response to NACT was an independent prognostic variable for recurrence-free and overall survival. Patients who did not achieve an overall optimal response had a 2.757-fold higher risk of recurrence and a 5.413-fold higher risk of death than those who obtained an overall optimal response.

Conclusions

Results appear to suggest that the chemo-surgical approach is an effective therapeutic option for patients with stage Ib2–IIb cervical cancer and that pathological response to NACT is the strongest prognostic factor for the outcome.