Gender Differences and Their Effects on Survival Outcomes in Lung Cancer Patients Treated With PD-1/PD-L1 Checkpoint Inhibitors: A Systematic Review and Meta-Analysis.

AIMS: Programmed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1) immune checkpoint inhibitors have had a major impact on the approach to care of patients with lung cancer. An important issue that is not known is whether they benefit men and women the same. We conducted a meta-analysis of all randomised controlled trials evaluating PD-1/PD-L1 inhibition in patients with non-small cell lung cancer (NSCLC) to determine if clinical response and survival are influenced by gender. MATERIALS AND METHODS: A PubMed search was carried out to identify all randomised controlled trials evaluating PD-1/PD-L1 inhibitors compared with conventional chemotherapy in NSCLC. Random-effects meta-analysis and meta-regression were performed to assess overall survival and progression-free survival (PFS) and whether there were differences in these outcomes between men and women. RESULTS: In total, 12 studies with data for overall survival and 11 studies with data for PFS were included. Immunotherapy showed a statistically significant benefit over chemotherapy for overall survival (pooled hazard ratio = 0.72, 95% confidence interval = 0.65-0.81, P < 0.001) and progression-free survival (pooled hazard ratio = 0.62, 95% confidence interval = 0.54-0.72, P < 0.001). We did not find a statistically significant difference between men and women in terms of overall survival (males versus females: pooled hazard ratio = 0.74, 95% confidence interval = 0.66-0.83 versus pooled hazard ratio = 0.72, 95% confidence interval = 0.63-0.82, P = 0.709) or progression-free survival (males versus females: pooled hazard ratio = 0.63, 95% confidence interval = 0.53-0.75 versus pooled hazard ratio = 0.72, 95% confidence interval = 0.58-0.88, P = 0.372). CONCLUSION: This is the first systematic review and meta-analysis investigating the effect of gender and response to PD-1/PD-L1 checkpoint inhibitors in patients solely with NSCLC. We examined 9270 and 6193 patients in terms of overall survival and PFS, respectively. Although there are significant biological differences between men's and women's immune responses, we have shown that these drugs offer the same survival benefit in patients with NSCLC regardless of gender.

The Development of an Antimicrobial Contact Lens - From the Laboratory to the Clinic.

Contact lens wear is generally safe and provides excellent vision. However, contact lens wear is often associated with the risk of developing ocular surface infection and inflammation, and in severe cases, the infection can result in loss of vision. Antimicrobial peptide-coated contact lenses have been made to help reduce the incidence of infection and inflammation. This paper reviews the research progress from conception, through the laboratory and preclinical tests to the latest information on clinical testing of an antimicrobial contact lens. We provide insights into the pathways followed and pitfalls that have been encountered. The journey has not always been linear or smooth, but has resulted in some of the first published clinical testing of antimicrobial peptide-coated contact lenses in humans. We hope this may help lead to the development and commercialisation of antimicrobial contact lenses in the future.

Retrospective study found that outpatient care for infants exposed to drugs during pregnancy was sustainable and safe.

AIM: We determined the safety, feasibility and sustainability of an outpatient model of care for infants exposed to intra-uterine drugs. METHODS: This was a retrospective chart review of 774 drug-exposed infants born between 1998 and 2016 at the Royal Hospital for Women, Sydney, Australia. RESULTS: Most (86%) of the mothers used multiple drugs, including opioids (58%). More than three-quarters (78%) of the infants were born full term at a mean gestation of 38 weeks and hospitalised for a median of seven days. This rose to 14 days if they were medicated for neonatal abstinence syndrome (NAS). Most of the NAS patients (83%) were discharged on medication, namely morphine, and the median duration of NAS treatment was 76 (interquartile range 35-120). Three medication errors occurred: two extra doses of phenobarbitone and one infant weaned off morphine faster than prescribed. No infants were rehospitalised for NAS. Four died from sudden infant death syndrome at 2.2-5.8 months after discharge and one drowned at 15 months. None were medicated at the time of death. CONCLUSION: Outpatient care for drug-exposed infants was sustainable and had low complication rates, even for those with NAS. The optimum duration of follow-up and impact on hospital costs should be examined.

Measuring Frequency Fluctuations in Nonlinear Nanomechanical Resonators.

Advances in nanomechanics within recent years have demonstrated an always expanding range of devices, from top-down structures to appealing bottom-up MoS2 and graphene membranes, used for both sensing and component-oriented applications. One of the main concerns in all of these devices is frequency noise, which ultimately limits their applicability. This issue has attracted a lot of attention recently, and the origin of this noise remains elusive to date. In this article we present a very simple technique to measure frequency noise in nonlinear mechanical devices, based on the presence of bistability. It is illustrated on silicon-nitride high-stress doubly clamped beams, in a cryogenic environment. We report on the same T/ f dependence of the frequency noise power spectra as reported in the literature. But we also find unexpected damping fluctuations, amplified in the vicinity of the bifurcation points; this effect is clearly distinct from already reported nonlinear dephasing and poses a fundamental limit on the measurement of bifurcation frequencies. The technique is further applied to the measurement of frequency noise as a function of mode number, within the same device. The relative frequency noise for the fundamental flexure δ f/ f0 lies in the range 0.5-0.01 ppm (consistent with the literature for cryogenic MHz devices) and decreases with mode number in the range studied. The technique can be applied to any type of nanomechanical structure, enabling progress toward the understanding of intrinsic sources of noise in these devices.

Interaction of the antimicrobial peptide melimine with bacterial membranes.

Melimine is a novel cationic peptide possessing broad-spectrum antimicrobial activity that is retained when attached to a surface, suggesting that interactions with bacterial membranes may be of primary importance to its activity. The effects of alterations in the environment on the conformation of melimine were investigated using circular dichroism and fluorescence spectra in membrane-mimetic solvents. Furthermore, the interactions of melimine with bacterial membranes of Pseudomonas aeruginosa and Staphylococcus aureus were examined using scanning electron and fluorescence microscopy, and perturbation of membrane integrity was tested by measurement of melimine-mediated diSC(3)-5 dye release from bacterial cells. Melimine has a predominantly random coil conformation that adopts a helical fold when exposed to organic solvents. However, when it is solubilised in micelles of sodium dodecyl sulphate, which are bacterial membrane-mimetic, the alpha-helical content increases to ca. 35-40%. A major effect of melimine was on the integrity of the cytoplasmic membrane both for P. aeruginosa and S. aureus. However, for P. aeruginosa the rapid loss of cytoplasmic membrane integrity correlated directly with loss of cell viability, whilst for S. aureus maximal dye release was obtained at concentrations where there was no significant loss of viability. There have been few studies to date investigating differences in the action of cationic peptides towards Gram-positive and Gram-negative bacteria. Consequently, further investigation of these mechanistic differences may allow more refined targeting of increasingly difficult-to-treat bacterial infections and/or further inform design of novel peptides with improved broad-spectrum activity.

Studies on animal schistosomes in Peninsular Malaysia: record of naturally infected animals and additional hosts of Schistosoma spindale.

Surveillance studies on cercarial dermatitis were carried out in paddy growing areas in Peninsular Malaysia. It was observed that dermatitis in paddy planters occurred in paddy fields which were cultivated using animals such as bafflos or fields where domestic animals were allowed to graze during the off planting season as these animals harbored the parasite. The causative agent of cercarial dermatitis was Schistosoma spindale. A total of 215 small mammals trapped from Alor Setar and 126 trapped from Labu were examined for the schistosome. In Alor Setar Bandicota indica, Rattus argentiventer and Rattus rattus diardii were the only wild mammals found to be infected with the parasite, while in the Labu areas only Rattus tiomanicus jalorensis was positive for the schistosome. The occurrence of S. spindale in R. argentiventer and R.r. diardii in Alor Setar and in R.t. jalorensis in Labu constitute new host and geographic distribution records of the schistosome.