Hereditary spastic paraplegia (HSP) is a set of genetic diseases caused by mutations in one of 72 genes that results in age-dependent corticospinal axon degeneration accompanied by spasticity and paralysis. Two genes implicated in HSPs encode proteins that regulate endoplasmic reticulum (ER) morphology. Atlastin 1 (ATL1, also known as SPG3A) encodes an ER membrane fusion GTPase and reticulon 2 (RTN2, also known as SPG12) helps shape ER tube formation. Here, we use a new fluorescent ER marker to show that the ER within wild-type Drosophila motor nerve terminals forms a network of tubules that is fragmented and made diffuse upon loss of the atlastin 1 ortholog atl. atl or Rtnl1 loss decreases evoked transmitter release and increases arborization. Similar to other HSP proteins, Atl inhibits bone morphogenetic protein (BMP) signaling, and loss of atl causes age-dependent locomotor deficits in adults. These results demonstrate a crucial role for ER in neuronal function, and identify mechanistic links between ER morphology, neuronal function, BMP signaling and adult behavior.
Urinary tract infections (UTIs) will affect most women, can recur especially in postmenopausal women, and can become antibiotic recalcitrant.
Escherichia coli
causes most community-acquired UTIs and recurrent UTIs. Current theories of virulence, based on studies of UTI-associated
E. coli
, propose multiple virulence mechanisms and complex host-pathogen interactions.
Objective:
Tamoxifen complicates management of conditions such as urinary tract infections (UTIs), urinary incontinence (UI), and/or pelvic organ prolapse (POP) that traditionally benefit from hormonal intake; thus, we reviewed our experience in managing these hormonally deprived women.
Materials and Methods:
After IRB approval, electronic medical records from women with current use or history of tamoxifen use and referred to a tertiary care center with female pelvic medicine and reconstructive surgery expertise for UTI, UI, and/or POP were reviewed.
Results:
From 2015 to 2020, 32 women treated with tamoxifen 10–40 mg for a median of 4 years were referred for UTIs (9), UI (10), symptomatic POP (8), or for a combination of these (5). Participants with UTI treated with antibiotics, prophylactic supplements, and/or electrofulguration had satisfactory response at median follow-up of 1 year (interquartile range [IQR]: 0.5–1). Ten of 15 women with UI chose intervention, with no self-reported UI recurrence at median follow-up of 2.5 years (IQR: 1–3). All but one participant with POP underwent vaginal or open/robotic mesh repairs, with satisfactory outcomes at median follow-up of 3 years (IQR: 2–7).
Conclusions:
The management of UTIs, UI, and POP in women on tamoxifen or unable to benefit from hormonal intake is challenging, but traditional interventions can be considered with satisfactory results.
KPN. The oral agents, cefuroxime, amoxicillin-clavulanate, TMP-SMX, and levofloxacin showed susceptibility rates ranging from 63.1% to 87.1% against ENT, EC, and KPN. TBP (MIC 50/90 , 0.12/0.12 mg/L) inhibited all PM at £0.25 mg/L. PM isolates were susceptible to ERT (100.0%), CAZ (98.7%), cefuroxime (94.4%), and amoxicillin/ clavulanate (96.6%), whereas susceptibility rates of 71.8-76.8% were noted for TMP-SMX and levofloxacin.CONCLUSIONS: TBP displayed potent activity against ENT UTI pathogens recovered from patients in the US. TBP demonstrated in vitro activity against these UTI pathogens similar to that of ERT. In addition, these data showed compromised activity of intravenous and oral agents used for treating UTI. This data supports the development of tebipenem as an oral option for management of UTI in the US.
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