The early neutrophil-committed progenitors aberrantly differentiate into immunoregulatory monocytes during emergency myelopoiesis.

Inflammatory stimuli cause a state of emergency myelopoiesis leading to neutrophil-like monocyte expansion. However, their function, the committed precursors, or growth factors remain elusive. In this study we find that Ym1+Ly6Chi monocytes, an immunoregulatory entity of neutrophil-like monocytes, arise from progenitors of neutrophil 1 (proNeu1). Granulocyte-colony stimulating factor (G-CSF) favors the production of neutrophil-like monocytes through previously unknown CD81+CX3CR1lo monocyte precursors. GFI1 promotes the differentiation of proNeu2 from proNeu1 at the cost of producing neutrophil-like monocytes. The human counterpart of neutrophil-like monocytes that also expands in response to G-CSF is found in CD14+CD16- monocyte fraction. The human neutrophil-like monocytes are discriminated from CD14+CD16- classical monocytes by CXCR1 expression and the capacity to suppress T cell proliferation. Collectively, our findings suggest that the aberrant expansion of neutrophil-like monocytes under inflammatory conditions is a process conserved between mouse and human, which may be beneficial for the resolution of inflammation.

Association of early physical activity time with pain, activities of daily living, and progression of vertebral body collapse in patients with vertebral compression fractures.

BACKGROUND: Physical activity can reduce pain and improve the ability to perform daily activities in patients with acute low back pain (LBP) due to various non-specific causes. The association between physical activity during the early phase of acute vertebral compression fractures (VCFs) and rehabilitation outcomes is unknown. AIM: The aim of this study was to investigate the effects of early physical activity time (EPAT) on pain following acute VCFs, recovery of the ability to perform activities of daily living (ADLs), and progression of fractured vertebral body collapse. DESIGN: Observational study. SETTING: Inpatient clinic. POPULATION: Sixty-nine patients with acute VCFs being treated conservatively at Nagasaki Memorial Hospital. METHODS: Physical activity was evaluated as the activity time corresponding to 1.8-8.3 metabolic equivalent activities measured by a motion-sensor during the first week after admission; it was defined as EPAT. The verbal rating scale (VRS) (0-4) at rest and during standing and walking and motor functional independence measure (mFIM) were assessed at weeks 0 (baseline), 2, and 4. Loss of vertebral height was measured in week 4. Mini-mental state examinations, trail making test part-A (TMT-A), and geriatric depression scale-15 were administered at baseline. Patients were divided into active (N.=35) and sedentary (N.=34) groups according to their median EPAT value during the first week. RESULTS: The completion times for TMT-A and mFIM scores at baseline as well as the relative functional gains of mFIM from baseline to week 2 or 4 were significantly associated with EPAT. VRS at rest and during standing and walking were not significantly different between the groups at week 2 and 4. Loss of vertebral height was not significantly different between the groups. CONCLUSIONS: EPAT in patients with acute VCF is associated with the recovery of the ability to perform ADLs. However, EPAT is associated with neither pain reduction nor progression of fractured vertebral body collapse. CLINICAL REHABILITATION IMPACT: This observational study indicates that physical activity in the early acute phase of VCF is associated with better recovery from acute VCF and would be an important factor for short-term recovery.

Cyclic muscle twitch contraction inhibits immobilization-induced muscle contracture and fibrosis in rats.

We investigated the effects of cyclic muscle twitch contraction caused by neuromuscular electrical stimulation (NMES) on immobilization-induced muscle contracture and fibrosis in rats. Twenty-nine rats were divided into control, immobilization, and immobilization with muscle contraction groups. The ankle joints of the immobilization and muscle contraction rats were fixed in full plantar flexion with a plaster cast for 4 weeks. In the muscle contraction group, cyclic muscle twitch contraction of the soleus muscle was induced using a commercial device (1 Hz, 4 ± 2 mA, 60 min/day, 5 times/week) with the ankle joint immobilized. The dorsiflexion range of ankle joint motion in the muscle contraction group was significantly greater than that in the immobilization group. The expressions of fibrosis-related genes (i.e., hypoxia inducible factor-1α, transforming growth factor-ß1, α-smooth muscle actin, and types I and III collagen) were significantly decreased in the muscle contraction group compared to the immobilization group. The fluorescence intensities of type I and type III collagen in the perimysium and endomysium in the muscle contraction group were significantly decreased compared to the immobilization group. These results suggest that cyclic muscle twitch contraction induced by NMES might alleviate skeletal muscle fibrosis, reducing immobilization-induced muscle contracture.

Enhancement of Shiga toxin production in enterohemorrhagic Escherichia coli serotype O157:H7 by DNase colicins.

Colicins are proteins produced by and active against several strains of Escherichia coli. Previously we reported that colicinogenic bacteria seemed beneficial in preventing the clinical manifestations of infectious disease caused by enterohemorrhagic E. coli O157 in humans. The inhibitory effects could be due to a decrease in O157 levels and/or pathogenicity. This study investigated the effects of colicinogenic E. coli on the production of Shiga toxin (Stx) by O157. Standard strains of colicinogenic bacteria carrying plasmids for each type of colicin (E3/5/8/9) were used for the study. The O157 strains were cultured in the presence of colicinogenic bacteria or extracted colicins. Compared with results for controls, DNase colicins (E8/9) facilitated an 8- to 64-fold increase in production of Stx2, while RNase colicins (E3/5) suppressed Stx production in only two strains. Stx prophages were induced in synchrony with Stx production. Semiquantitative real-time reverse transcription-PCR (RT-PCR) was then performed to examine SOS gene expression. The RT-PCR results clearly indicated a marked increase in mRNA levels of SOS reaction-associated genes after the addition of DNase colicins. We believe that Stx prophages are induced by the SOS response to DNA damage caused by DNase colicins, thus leading to higher Stx production. These findings suggest that while colicinogenic bacteria can be antagonistic to O157 infection, DNase colicins may enhance Stx production. Thus, colicinogenic flora is likely to be involved in the complex pathogenic pathways of O157 infection, and further investigation should be performed before the use of colicinogenic bacteria as an intervention method.