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Fusobacterium nucleatum is an important oral bacterium that has been linked to the development of chronic diseases such as periodontitis and colorectal cancer. In periodontal disease, F. nucleatum forms the backbone of the polymicrobial biofilm and in colorectal cancer is implicated in aetiology, metastasis and chemotherapy resistance. The control of this bacteria may be important in assisting treatment of these diseases. With increased rates of antibiotic resistance globally, there is need for development of alternatives such as bacteriophages, which may complement existing therapies. Here we describe the morphology, genomics and functional characteristics of FNU1, a novel bacteriophage lytic against F. nucleatum. Transmission electron microscopy revealed FNU1 to be a large Siphoviridae virus with capsid diameter of 88 nm and tail of approximately 310 nm in length. Its genome was 130914 bp, with six tRNAs, and 8% of its ORFs encoding putative defence genes. FNU1 was able to kill cells within and significantly reduce F. nucleatum biofilm mass. The identification and characterisation of this bacteriophage will enable new possibilities for the treatment and prevention of F. nucleatum associated diseases to be explored.
Subject terms: Colon cancer, Biofilms, Infection control in dentistry, Bacteriophages, Applied microbiology
Genomic, morphological and functional characterisation of novel bacteriophage FNU1 capable of disrupting Fusobacterium nucleatum biofilms
Mwila Kabwe,1 Teagan L. Brown,1 Stuart Dashper,2 Lachlan Speirs,1 Heng Ku,1 Steve Petrovski,3 Hiu Tat Chan,4 Peter Lock,5 and Joseph Tuccicorresponding author1
The nasopharyngeal tract traps mainly coarse particles in inhaled air. Soluble carcinogenic compounds, endotoxins, and trace metals contained in these particles are potential causes of inflammation and oxidative stress which could enhance carcinogenesis. The aim of this study was to determine the association between coarse particulate matter (PM10-2.5) and nasopharyngeal cancer (NPC). A total of 521,098 men (355 cases and 520,743 non-cases), aged ≥40 years were included in this study. Data were retrieved from the Taiwan Cancer Registry, the Adult Preventive Medical Services Database, and the Air Quality Monitoring Database. PM10-2.5 was significantly associated with a higher risk of NPC after adjusting for SO2, NOx, O3, age, body mass index, smoking, alcohol drinking, betel nut chewing, exercise, hypertension, diabetes, and hyperlipidemia. With PM10-2.5<20.44 μg/m3 as the reference, the ORs and 95% CIs were 1.47; 1.03-2.11, 1.34; 0.94-1.91, and 1.68; 1.16-2.44 for 20.44≤PM10-2.5<24.08, 24.08≤PM10-2.5<29.27, and PM10-2.5≥29.27 μg/m3, respectively. PM10-2.5 remained significantly associated with a higher risk of NPC after further adjustments were made for the aforementioned covariates and PM2.5. The ORs; 95% CIs were 1.42; 0.96 to 2.12, 1.41; 0.94 to 2.10, and 1.71; 1.10 to 2.66 for 20.44≤PM10-2.5<24.08, 24.08≤PM10-2.5<29.27, and PM10-2.5≥29.27 μg/m3, respectively. In conclusion, PM10-2.5 was significantly associated with a higher risk of NPC in Taiwanese men.
nasal cavity, cancer, neoplasms, respiratory tract diseases
Association between coarse particulate matter (PM10-2.5) and nasopharyngeal carcinoma among Taiwanese men
Hsu-Chih Huang,1,2 Disline Manli Tantoh,3,4 Shu-Yi Hsu,4 Oswald Ndi Nfor,4 Cheau-Feng Lin Frank,2,5 Chia-Chi Lung,4 Chien-Chang Ho,6 Chih-Yi Chen,corresponding author1,2 and Yung-Po Liawcorresponding author3,4
Premenstrual syndrome (PMS) is a psychological and somatic disorder of unknown aetiology, with symptoms typically including irritability, depression, mood swings, bloating, breast tenderness and sleep disturbances. About 3% to 10% of women who experience these symptoms may also meet criteria for premenstrual dysphoric disorder (PMDD). PMS symptoms recur during the luteal phase of the menstrual cycle and reduce by the end of menstruation. PMS results from ovulation and may be due to ovarian steroid interactions relating to neurotransmitter dysfunction. Premenstrual disorders have a devastating effect on women, their families and their work.
Several treatment options have been suggested for PMS, including pharmacological and surgical interventions. The treatments thought to be most effective tend to fall into one of two categories: suppressing ovulation or correcting a speculated neuroendocrine anomaly.
Transdermal oestradiol by patch, gel or implant effectively stops ovulation and the cyclical hormonal changes which produce the cyclical symptoms. These preparations are normally used for hormone therapy and contain lower doses of oestrogen than found in oral contraceptive pills. A shortened seven?day course of a progestogen is required each month for endometrial protection but can reproduce premenstrual syndrome?type symptoms in these women.
To determine the effectiveness and safety of non?contraceptive oestrogen?containing preparations in the management of PMS.
On 14 March 2016, we searched the following databases: the Cochrane Gynaecology and Fertility Group (CGF) Specialised Register; Cochrane Central Register of Studies (CRSO); MEDLINE; Embase; PsycINFO; CINAHL; ClinicalTrials.gov; metaRegister of Controlled trials (mRCT); and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) Search Portal. In addition, we checked the reference lists of articles retrieved.
We included published and unpublished randomized placebo or active controlled trials on the efficacy of the use of non?contraceptive oestrogen?containing preparations in the management of premenstrual syndrome in women of reproductive age with PMS diagnosed by at least two prospective cycles without current psychiatric disorder.
Data collection and analysis
Two review authors independently selected studies, assessed risk of bias, extracted data on premenstrual symptoms and adverse effects and entered data into Review Manager 5 software. Where possible, intention?to?treat or modified intention?to?treat analysis was used. Studies were pooled using a fixed?effect model, analysing cross?over trials as parallel trials. Standardised mean differences (SMDs) with 95% confidence intervals (CIs) were calculated for premenstrual symptom scores. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated for dichotomous outcomes. The overall quality of the evidence was assessed using the GRADE working group methods.
The search resulted in 524 potentially relevant articles. Five eligible randomized controlled trials (RCTs) were identified (305 women). Trials using oral tablets, transdermal patches and implants were identified. No trial used gels.
One small cross?over trial (11 women, effective sample size 22 women considering cross?over trials) compared oral luteal?phase oestrogen versus placebo. Data were very low quality and unsuitable for analysis, but study authors reported that the intervention was ineffective and might aggravate the symptoms of PMS. They also reported that there were no adverse events.
Three studies compared continuous oestrogen with progestogen versus placebo (with or without progestogen). These trials were of reasonable quality, although with a high risk of attrition bias and an unclear risk of bias due to potential carry?over effects in two cross?over trials. Continuous oestrogen had a small to moderate positive effect on global symptom scores (SMD ?0.34, 95% CI ?0.59 to ?0.10, P = 0.005, 3 RCTs, 158 women, effective sample size 267 women, I² = 63%, very low quality evidence). The evidence was too imprecise to determine if the groups differed in withdrawal rates due to adverse effects (RR 0.64, 95% CI 0.26 to 1.58, P = 0.33, 3 RCTs, 196 women, effective sample size 284 women, I² = 0%, very low quality evidence). Similarly, the evidence was very imprecise in measures of specific adverse events, with large uncertainties around the true value of the relative risk. None of the studies reported on long?term risks such as endometrial cancer or breast cancer.
One study compared patch dosage (100 vs 200 ?g oestrogen, with progestogen in both arms) and had a high risk of performance bias, detection bias and attrition bias. The study did not find evidence that dosage affects global symptoms but there was much uncertainty around the effect estimate (SMD ?1.55, 95% CI ?8.88 to 5.78, P = 0.68, 1 RCT, 98 women, very low quality evidence). The evidence on rates of withdrawal for adverse events was too imprecise to draw any conclusions (RR 0.70, 95% CI 0.34 to 1.46, P = 0.34, 1 RCT, 107 women, low?quality evidence). However, it appeared that the 100 ?g dose might be associated with a lower overall risk of adverse events attributed to oestrogen (RR 0.51, 95% Cl 0.26 to 0.99, P = 0.05, 1 RCT, 107 women, very low quality evidence) with a large uncertainty around the effect estimate.
The overall quality of the evidence for all comparisons was very low, mainly due to risk of bias (specifically attrition), imprecision, and statistical and clinical heterogeneity.
We found very low quality evidence to support the effectiveness of continuous oestrogen (transdermal patches or subcutaneous implants) plus progestogen, with a small to moderate effect size. We found very low quality evidence from a study based on 11 women to suggest that luteal?phase oral unopposed oestrogen is probably ineffective and possibly detrimental for controlling the symptoms of PMS. A comparison between 200 ?g and 100 ?g doses of continuous oestrogen was inconclusive with regard to effectiveness, but suggested that the lower dose was less likely to cause side effects. Uncertainty remains regarding safety, as the identified studies were too small to provide definite answers. Moreover, no included trial addressed adverse effects that might occur beyond the typical trial duration of 2?8 months. This suggests the choice of oestrogen dose and mode of administration could be based on an individual woman’s preference and modified according to the effectiveness and tolerability of the chosen regimen.
Female, Humans, Administration, Oral, Drug Implants, Drug Therapy, Combination, Estrogens, Estrogens/administration & dosage, Estrogens/adverse effects, Luteal Phase, Premenstrual Dysphoric Disorder, Premenstrual Dysphoric Disorder/drug therapy, Premenstrual Syndrome, Premenstrual Syndrome/drug therapy, Progestins, Randomized Controlled Trials as Topic, Transdermal Patch
Non?contraceptive oestrogen?containing preparations for controlling symptoms of premenstrual syndrome
Bushra Naheed,corresponding author Jan Herman Kuiper, Olalekan A Uthman, Fidelma O'Mahony, and Patrick Michael Shaughn O'Brien