A New Perspective to Interpret How the Vestibular Efferent System Correlates the Complexity of Routine Balance Maintenance with Management of Emergency Fall Prevention Strategies.

Bipedalism is unique among mammals. Until modern times, a fall and resulting leg fracture could be fatal. Balance maintenance after a destabilizing event requires instantaneous decision making. The vestibular system plays an essential role in this process, initiating an emergency response. The afferent otolithic neural response is the first directionally oriented information to reach the cortex, and it can then be used to initiate an appropriate protective response. Some vestibular efferent axons feed directly into type I vestibular hair cells. This allows for rapid vestibular feedback via the striated organelle (STO), which has been largely ignored in most texts. We propose that this structure is essential in emergency fall prevention, and also that the system of sensory detection and resultant motor response works by having efferent movement information simultaneously transmitted to the maculae with the movement commands. This results in the otolithic membrane positioning itself precisely for the planned movement, and any error is due to an unexpected external cause. Error is fed back via the vestibular afferent system. The efferent system causes macular otolithic membrane movement through the STO, which occurs simultaneously with the initiating motor command. As a result, no vestibular afferent activity occurs unless an error must be dealt with.

Effect of transdermal drug delivery patches on the stratum corneum: in vivo inspection with a handheld terahertz probe.

Transdermal drug delivery patches are a good alternative to hypodermic drug injection. The drug delivery efficiency depends strongly on the hydration of the skin under treatment, and therefore, it is essential to study the effects on the skin induced by the application of these medical-grade patches. Terahertz (THz) spectroscopy shows great promise for non-invasive skin evaluation due to its high sensitivity to subtle changes in water content, low power and non-ionizing properties. In this work, we study the effects of transdermal drug delivery patches (three fully occlusive and three partially occlusive) applied on the upper arms of ten volunteers for a maximum period of 28 h. Three different levels of propylene glycol (0 %, 3 % and 6 %) are added to the patches as excipient. By performing multilayer analysis, we successfully retrieve the water content of the stratum corneum (SC) which is the outermost layer of skin, as well as its thickness at different times before and after applying the patches. This study demonstrates the potential of using THz sensing for non invasive skin monitoring and has wide applications for skin evaluation as well as the development of skin products.

Neonatal Phototherapy-The Need to Measure and Document.

This Viewpoint discusses the need for universal standards of recording and measuring phototherapy administered to infants to monitor for potential adverse effects in the long term.

Interval post-colonoscopy colorectal cancer following a negative colonoscopy in a fecal immunochemical test-based screening program.

BACKGROUND: In the Dutch colorectal (CRC) screening program, fecal immunochemical test (FIT)-positive individuals are referred for colonoscopy. If no relevant findings are detected at colonoscopy, individuals are reinvited for FIT screening after 10 years. We aimed to assess CRC risk after a negative colonoscopy in FIT-positive individuals. METHODS: In this cross-sectional cohort study, data were extracted from the Dutch national screening information system. Participants with a positive FIT followed by a negative colonoscopy between 2014 and 2018 were included. A negative colonoscopy was defined as a colonoscopy during which no more than one nonvillous, nonproximal adenoma < 10 mm or serrated polyp < 10 mm was found. The main outcome was interval post-colonoscopy CRC (iPCCRC) risk. iPCCRC risk was reviewed against the risk of interval CRC after a negative FIT (FIT IC) with a 2-year screening interval. RESULTS: 35 052 FIT-positive participants had a negative colonoscopy and 24 iPCCRCs were diagnosed, resulting in an iPCCRC risk of 6.85 (95 %CI 4.60-10.19) per 10 000 individuals after a median follow-up of 1.4 years. After 2.5 years of follow-up, age-adjusted iPCCRC risk was approximately equal to FIT IC risk at 2 years. CONCLUSION: Risk of iPCCRC within a FIT-based CRC screening program was low during the first years after colonos-copy but, after 2.5 years, was the same as the risk in FIT-negative individuals at 2 years, when they are reinvited for screening. Colonoscopy quality may therefore require further improvement and FIT screening interval may need to be reduced after negative colonoscopy.

A Desmethylphosphinothricin Dipeptide Derivative Effectively Inhibits Escherichia coli and Bacillus subtilis Growth.

New antibiotics are unquestionably needed to fight the emergence and spread of multidrug-resistant bacteria. To date, antibiotics targeting bacterial central metabolism have been poorly investigated. By determining the minimal inhibitory concentration (MIC) of desmethylphosphinothricin (Glu-γ-PH), an analogue of glutamate with a phosphinic moiety replacing the γ-carboxyl group, we previously showed its promising antibacterial activity on Escherichia coli. Herein, we synthetized and determined the growth inhibition exerted on E. coli by an L-Leu dipeptide derivative of Glu-γ-PH (L-Leu-D,L-Glu-γ-PH). Furthermore, we compared the growth inhibition obtained with this dipeptide with that exerted by the free amino acid, i.e., Glu-γ-PH, and by their phosphonic and non-desmethylated analogues. All the tested compounds were more effective when assayed in a chemically-defined minimal medium. The dipeptide L-Leu-D,L-Glu-γ-PH had a significantly improved antibacterial activity (2 µg/mL), at a concentration between the non-desmethytaled (0.1 µg/mL) and the phosphonic (80 µg/mL) analogues. Also, in Bacillus subtilis, the dipeptide L-Leu-D,L-Glu-γ-PH displayed an activity comparable to that of the antibiotic amoxicillin. This work highlights the antibacterial relevance of the phosphinic pharmacophore and proposes new avenues for the development of novel antimicrobial drugs containing the phosphinic moiety.

A probable koala from the Oligocene of central Australia provides insights into early diprotodontian evolution.

Diprotodontians are the morphologically and ecologically most diverse order of marsupials. However, an approximately 30-million-year gap in the Australian terrestrial vertebrate fossil record means that the first half of diprotodontian evolution is unknown. Fossil taxa from immediately either side of this gap are therefore critical for reconstructing the early evolution of the order. Here we report the likely oldest-known koala relatives (Phascolarctidae), from the late Oligocene Pwerte Marnte Marnte Local Fauna (central Australia). These include coeval species of Madakoala and Nimiokoala, as well as a new probable koala (?Phascolarctidae). The new taxon, Lumakoala blackae gen. et sp. nov., was comparable in size to the smallest-known phascolarctids, with body-mass estimates of 2.2-2.6 kg. Its bunoselenodont upper molars retain the primitive metatherian condition of a continuous centrocrista, and distinct stylar cusps B and D which lacked occlusion with the hypoconid. This structural arrangement: (1) suggests a morphocline within Phascolarctidae from bunoselenodonty to selenodonty; and (2) better clarifies the evolutionary transitions between molar morphologies within Vombatomorphia. We hypothesize that the molar form of Lumakoala blackae approximates the ancestral condition of the suborder Vombatiformes. Furthermore, it provides a plausible link between diprotodontians and the putative polydolopimorphians Chulpasia jimthorselli and Thylacotinga bartholomaii from the early Eocene Tingamarra Local Fauna (eastern Australia), which we infer as having molar morphologies consistent with stem diprotodontians.

C-Methylated Spermidine Derivatives: Convenient Syntheses and Antizyme-Related Effects.

The biogenic polyamines, spermidine (Spd) and spermine (Spm), are present at millimolar concentrations in all eukaryotic cells, where they participate in the regulation of vitally important cellular functions. Polyamine analogs and derivatives are a traditional and important instrument for the investigation of the cellular functions of polyamines, enzymes of their metabolism, and the regulation of the biosynthesis of antizyme-a key downregulator of polyamine homeostasis. Here, we describe convenient gram-scale syntheses of a set of C-methylated analogs of Spd. The biochemical properties of these compounds and the possibility for the regulation of their activity by moving a methyl group along the polyamine backbone and by changing the stereochemistry of the chiral center(s) are discussed.