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Transitory appearance of immune suppressive polymorphonuclear neutrophils (PMNs) defined as myeloid-derived suppressor cells (PMNs-MDSCs) in newborns is important for their protection from inflammation associated with newly established gut microbiota. Here, we report that inhibition of the type I IFN (IFN1) pathway played a major role in regulation of PMNs-MDSCs-suppressive activity during first weeks of life. Expression of the IFN1 receptor IFNAR1 was markedly lower in PMNs-MDSCs. However, in newborn mice, down-regulation of IFNAR1 was not sufficient to render PMNs immune suppressive. That also required the presence of a positive signal from lactoferrin via its receptor low-density lipoprotein receptor-related protein 2. The latter effect was mediated via NF-κB activation, which was tempered by IFN1 in a manner that involved suppressor of cytokine signaling 3. Thus, we discovered a mechanism of tight regulation of immune suppressive PMNs-MDSCs in newborns, which may be used in the development of therapies of neonatal pathologies., (©2022 Society for Leukocyte Biology.)

Background: Slips, trips and falls (STF) are a major cause of workplace injury., Aims: To examine risk factors for STF at a large US chemical manufacturing company., Methods: We conducted a case-control study of occupational STF. Cases were identified from company injury records between 1 April 2009 and 1 May 2011. Four controls per case were randomly selected from all active company workers employed during the same time. Data were collected through a questionnaire and from company medical examinations. Logistic regression was used to calculate odds ratio (OR) and 95% confidence intervals (95% CI) for personal, environmental and health-related risk factors for STF., Results: There were 74 cases and 309 controls. The response rate was 65% for the cases and 68% for the controls. Most STF were unrelated to production activities. When examining all factors in a logistic regression model, increased OR were observed for increased body mass index (OR = 1.44, 95% CI: 1.03-2.02), having arthritis (OR = 2.11, 95% CI: 1.01-4.37), lack of exercise (OR = 2.25, 95% CI: 1.01-5.05), carrying materials (OR = 3.01, 95% CI: 1.41-6.43) and being female (OR = 2.46, 95% CI: 1.17-5.19). Reduced risk of STF was observed for never having smoked (OR = 0.48, 95% CI: 0.24-0.95), long service (OR = 0.53, 95% CI: 0.34-0.81) and persons working over 8h a day (OR = 0.42, 95% CI: 0.20-0.88)., Conclusions: Risk factors for STF in a large US chemical company are similar to those reported from other workplaces, but we found that staying fit and healthy is important for reducing risk.

Ductal carcinoma in situ (DCIS) is the fastest growing subtype of breast cancer, mainly because of the aging of our populations and improvements in diagnostic mammography and core biopsy. DCIS represents a proliferation of malignant-appearing cells that have not invaded beyond the ductal basement membrane and is a precursor for the development of invasive breast cancer (IBC). Approximately 40% of patients with DCIS treated with biopsy alone, without complete excision or further therapy, develop IBC. Most DCIS itself is harmless if it is detected and excised before it can progress to IBC, and the current approach to DCIS treatment is aimed at just that goal. Typically, it consists of multimodal treatment including segmental mastectomy followed by radiation therapy to the whole breast and then hormonal therapy or total mastectomy followed by hormonal therapy. This review discusses the state-of-the-art in DCIS detection and treatment and highlights promising new strategies in the care of DCIS patients. The data regarding the effectiveness of breast-conserving surgery versus total mastectomy, the possible avoidance of radiation therapy in some subgroups of patients, and the role of hormonal agents are reviewed. Neoadjuvant therapy and the use of trastuzumab for DCIS are currently under investigation and may be future treatment options for DCIS.

The pyrimidine nucleotide biosynthesis (pyr) operon in Bacillus subtilis is regulated by transcriptional attenuation. The PyrR protein binds in a uridine nucleotide-dependent manner to three attenuation sites at the 5'-end of pyr mRNA. PyrR binds an RNA-binding loop, allowing a terminator hairpin to form and repressing the downstream genes. The binding of PyrR to defined RNA molecules was characterized by a gel mobility shift assay. Titration indicated that PyrR binds RNA in an equimolar ratio. PyrR bound more tightly to the binding loops from the second (BL2 RNA) and third (BL3 RNA) attenuation sites than to the binding loop from the first (BL1 RNA) attenuation site. PyrR bound BL2 RNA 4-5-fold tighter in the presence of saturating UMP or UDP and 150- fold tighter with saturating UTP, suggesting that UTP is the more important co-regulator. The minimal RNA that bound tightly to PyrR was 28 nt long. Thirty-one structural variants of BL2 RNA were tested for PyrR binding affinity. Two highly conserved regions of the RNA, the terminal loop and top of the upper stem and a purine-rich internal bulge and the base pairs below it, were crucial for tight binding. Conserved elements of RNA secondary structure were also required for tight binding. PyrR protected conserved areas of the binding loop in hydroxyl radical footprinting experiments. PyrR likely recognizes conserved RNA sequences, but only if they are properly positioned in the correct secondary structure.