Equivalence of background and bleaching desensitization in isolated rod photoreceptors of the larval tiger salamander.

Psychophysical experiments have shown an equivalence between sensitivity reduction by background light and by bleaches for the human scotopic system. We have compared the effects of backgrounds and bleaches on the light-sensitive membrane-current responses of isolated rod photoreceptors from the salamander Ambystoma tigrinum. The quantum catch loss was factored out from the desensitization due to bleaching to give the fraction of "extra" desensitization due to adaptation. For backgrounds, desensitization is well described by the Weber/Fechner equation. The extra desensitization after bleaches can also be described by the Weber/Fechner equation, if an "equivalent" background produced by bleaching is made linearly proportional to the fraction of pigment bleached. A background which produces an extra desensitization of a factor of two is equivalent to a fractional bleach of approximately 6%. Equivalent background and bleaching desensitizations were associated with similar reductions in circulating current. There is a linear relation between log flash sensitivity and decrease in circulating current. Equivalent background and bleaching desensitizations were associated with similar increases in cGMP phosphodiesterase and guanylate cyclase activity. These were inferred from membrane current changes after steps into lithium or IBMX solutions. There were also similar reductions in the integration times of dim flash responses for equivalent desensitizations produced by backgrounds and bleaches. These results suggest that the equivalence between background and bleaching found psychophysically may arise at the very earliest stages of visual processing and that these two processes of desensitization have similar underlying mechanisms

Impaired clearance of ceftizoxime and cefotaxime after orthotopic liver transplantation.

The pharmacokinetics of ceftizoxime (CZX) and of cefotaxime (CTX) were studied in five children and five adults after orthotopic liver transplantation (OLT). Delayed clearance of CZX (clearance of 0.21 to 1.26 ml/min per kg [body weight]) and CTX (clearance of 0.40 to 1.49 ml/min per kg) occurred in 7 of the 10 OLT patients. We conclude that abnormal CZX and CTX clearance is common after OLT and may be associated with minimal change in serum creatinine

Probabilistic design of a molybdenum-base alloy using a neural network

An artificial intelligence tool is exploited to discover and characterize a new molybdenum-base alloy that is the most likely to simultaneously satisfy targets of cost, phase stability, precipitate content, yield stress, and hardness. Experimental testing demonstrates that the proposed alloy fulfills the computational predictions, and furthermore the physical properties exceed those of other commercially available Mo-base alloys for forging-die applications.The authors acknowledge the financial support of Rolls-Royce plc, EPSRC under EP/H022309/1 and EP/H500375/1, the Royal Society, and Gonville & Caius College

Simple non-mydriatic retinal photography is feasible and demonstrates retinal microvascular dilation in Chronic Obstructive Pulmonary Disease (COPD).

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is associated with an increased risk of myocardial infarction and stroke but it remains unclear how to identify microvascular changes in this population. OBJECTIVES: We hypothesized that simple non-mydriatic retinal photography is feasible and can be used to assess microvascular damage in COPD. METHODS: Novel Vascular Manifestations of COPD was a prospective study comparing smokers with and without COPD, matched for age. Non-mydriatic, retinal fundus photographs were assessed using semi-automated software. RESULTS: Retinal images from 24 COPD and 22 control participants were compared. Cases were of similar age to controls (65.2 vs. 63.1 years, p = 0.38), had significantly lower Forced Expiratory Volume in one second (FEV1) (53.4 vs 100.1% predicted; p < 0.001) and smoked more than controls (41.7 vs. 29.6 pack years; p = 0.04). COPD participants had wider mean arteriolar (155.6 ±15 uM vs. controls [142.2 ± 12 uM]; p = 0.002) and venular diameters (216.8 ±20.7 uM vs. [201.3± 19.1 uM]; p = 0.012). Differences in retinal vessel caliber were independent of confounders, odds ratios (OR) = 1.08 (95% confidence intervals [CI] = 1.02, 1.13; p = 0.007) and OR = 1.05 (CI = 1.01, 1.09; p = 0.011) per uM increase in arteriolar and venular diameter respectively. FEV1 remained significantly associated with retinal vessel dilatation r = -0.39 (p = 0.02). CONCLUSIONS: Non-mydriatic retinal imaging is easily facilitated. We found significant arteriole and venous dilation in COPD compared to age-matched smokers without COPD associated with lung function independent of standard cardiovascular risk factors. Retinal microvascular changes are known to be strongly associated with future vascular events and retinal photography offers potential to identify this risk. TRIAL REGISTRATION: clinicaltrials.gov NCT02060292

The relationship between reductions in knee loading and immediate pain response whilst wearing lateral wedged insoles in knee osteoarthritis

Studies of lateral wedge insoles (LWIs) in medial knee osteoarthritis (OA) have shown reductions in the average external knee adduction moment (EKAM) but no lessening of knee pain. Some treated patients actually experience increases in the EKAM which could explain the overall absence of pain response. We examined whether, in patients with painful medial OA, reductions in the EKAM were associated with lessening of knee pain. Each patient underwent gait analysis whilst walking in a control shoe and two LWI's. We evaluated the relationship between change in EKAM and change in knee pain using Spearman Rank Correlation coefficients and tested whether dichotomizing patients into biomechanical responders (decreased EKAM) and non-responders (increased EKAM) would identify those with reductions in knee pain. In 70 patients studied, the EKAM was reduced in both LWIs versus control shoe (−5.21% and −6.29% for typical and supported wedges, respectively). The change in EKAM using LWIs was not significantly associated with the direction of knee pain change. Further, 54% were biomechanical responders, but these persons did not have more knee pain reduction than non-responders. Whilst LWIs reduce EKAM, there is no clearcut relationship between change in medial load when wearing LWIs and corresponding change in knee pain

Field cancerization in breast cancer

Breast cancer affects one in seven women worldwide during their lifetime. Widespread mammographic screening programs and education campaigns allow for early detection of the disease, often during its asymptomatic phase. Current practice in treatment and recurrence monitoring is based primarily on pathological evaluations but can also encompass genomic evaluations, both of which focus on the primary tumor. Although breast cancer is one of the most studied cancers, patients still recur at a rate of up to 15% within the first 10 years post‐surgery. Local recurrence was originally attributed to tumor cells contaminating histologically normal (HN) tissues beyond the surgical margin, but advances in technology have allowed for the identification of distinct aberrations that exist in the peri‐tumoral tissues themselves. One leading theory to explain this phenomenon is the field cancerization theory. Under this hypothesis, tumors arise from a field of molecularly altered cells that create a permissive environment for malignant evolution, which can occur with or without morphological changes. The traditional histopathology paradigm dictates that molecular alterations are reflected in the tissue phenotype. However, the spectrum of inter‐patient variability of normal breast tissue may obfuscate recognition of a cancerized field during routine diagnostics. In this review, we explore the concept of field cancerization focusing on HN peri‐tumoral tissues: we present the pathological and molecular features of field cancerization within these tissues and discuss how the use of peri‐tumoral tissues can affect research. Our observations suggest that pathological and molecular evaluations could be used synergistically to assess risk and guide the therapeutic management of patients. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland

A Review of Wearable Sensor Systems to Monitor Plantar Loading in the Assessment of Diabetic Foot Ulcers

Diabetes is highly prevalent throughout the world and imposes a high economic cost on countries at all income levels. Foot ulceration is one devastating consequence of diabetes, which can lead to amputation and mortality. Clinical assessment of diabetic foot ulcer (DFU) is currently subjective and limited, impeding effective diagnosis, treatment and prevention. Studies have shown that pressure and shear stress at the plantar surface of the foot plays an important role in the development of DFUs. Quantification of these could provide an improved means of assessment of the risk of developing DFUs. However, commercially-available sensing technology can only measure plantar pressures, neglecting shear stresses and thus limiting their clinical utility. Research into new sensor systems which can measure both plantar pressure and shear stresses are thus critical. Our aim in this paper is to provide the reader with an overview of recent advances in plantar pressure and stress sensing and offer insights into future needs in this critical area of healthcare. Firstly, we use current clinical understanding as the basis to define requirements for wearable sensor systems capable of assessing DFU. Secondly, we review the fundamental sensing technologies employed in this field and investigate the capabilities of the resultant wearable systems, including both commercial and research-grade equipment. Finally, we discuss research trends, ongoing challenges and future opportunities for improved sensing technologies to monitor plantar loading in the diabetic foot