Cryotherapy Treatment of Cutaneous Kaposi Sarcoma in a Patient With B-Cell Chronic Lymphocytic Leukemia: A Case Report and Short Review of the Literature.

INTRODUCTION: Kaposi sarcoma (KS) is a low-grade mesenchymal tumor involving the blood and the lymphatic vessels that primarily effaces the skin and is mediated by human herpesvirus-8 (HHV-8) in more than 90% of patients. There are 4 distinct types of KS. Compared with the classic and AIDS-related variants, chronic lymphocytic leukemia (CLL) associated with KS is a relatively rare clinical condition; thus, only a few cases have been reported. CASE REPORT: This report presents a case study of an 87-year-old patient with B-cell CLL and cutaneous KS managed with cryotherapy, along with a short review of the literature. CONCLUSIONS: Considering that the method is relatively simple and with few adverse effects, cryotherapy may represent a simple and safe treatment method for cutaneous KS. However, more studies should be conducted to further evaluate the effectiveness of cryotherapy as a promising treatment for cutaneous KS.

The Use of Robotics in Surgery of Benign Liver Diseases: A Systematic Review.

BACKGROUND: Surgical treatment of benign liver diseases (BLD) remains a field of conflict, due to increased risk and high complication rate. However, the introduction of minimally invasive surgery has led to increased number of patients with BLD being treated surgically, with similar outcomes and fewer complications. Current data support the application of laparoscopic surgery (LS) and robotic surgery (RS) in surgical treatment of liver malignancies, but there are insufficient data concerning the application of robotic surgery in BLD. In the present systematic review, we aimed to evaluate the application of RS in BLD surgery. METHODS: After a thorough search of Medline, Scopus, and Cochrane Library, 12 studies were considered eligible with a total number of 115 patients with BLD. DISCUSSION: In brief, RS appears to be a safe and feasible option for BLD surgery. When compared to open surgery, RS is associated with lower blood loss, shorter length of stay, and fewer complication rate. Regarding LS, the peri- and postoperative outcomes were similar, but RS can overcome the technical limitations of LS. However, the cost of RS remains a major drawback in its widespread application. CONCLUSIONS: Considering our findings, RS can be a safe and feasible option for BLD surgery, but further studies are needed to justify the introduction of RS in liver surgery and to define the type of patients that will benefit the most from it.

Analyzing Acute Care Surgery Patient Flow in the Emergency Department During COVID-19 Pandemic.

During the COVID-19 pandemic, the number of visits in emergency departments (ED) worldwide decreased significantly based on several studies. This study aims to compare the patient flow in the emergency surgery department during the COVID-19 pandemic and a control period in the emergency department of a public tertiary care hospital in Greece. The overall patient flow reduction regarding the ED visits between the two examined periods was 49.07%. The emergency surgery department's corresponding visits were 235 and 552, respectively, which indicated an overall patient flow decrease of 57.43%. Chi-square analysis showed that age groups and ambulance use had statistically significant associations with the periods examined. An independent samples t-test was applied and deduced that the average patient's age was statistically significantly higher in the COVID-19 pandemic than in the non-pandemic period. By analyzing hospital information system data, useful conclusions can be drawn to prepare a surgical emergency unit better and optimize resource allocation in a healthcare facility in similar critical situations.

A Patient with Dysphagia.

We report a case of an uncommon type of dysphagia, due to esophagus compression by an aberrant right subclavian artery. This condition, known as dysphagia lusoria, was first recorded in 1787 by London physician David Bayford.

Quantitative Kinetic Models from Intravital Microscopy: A Case Study Using Hepatic Transport.

The liver performs critical physiological functions, including metabolizing and removing substances, such as toxins and drugs, from the bloodstream. Hepatotoxicity itself is intimately linked to abnormal hepatic transport, and hepatotoxicity remains the primary reason drugs in development fail and approved drugs are withdrawn from the market. For this reason, we propose to analyze, across liver compartments, the transport kinetics of fluorescein-a fluorescent marker used as a proxy for drug molecules-using intravital microscopy data. To resolve the transport kinetics quantitatively from fluorescence data, we account for the effect that different liver compartments (with different chemical properties) have on fluorescein's emission rate. To do so, we develop ordinary differential equation transport models from the data where the kinetics is related to the observable fluorescence levels by "measurement parameters" that vary across different liver compartments. On account of the steep non-linearities in the kinetics and stochasticity inherent to the model, we infer kinetic and measurement parameters by generalizing the method of parameter cascades. For this application, the method of parameter cascades ensures fast and precise parameter estimates from noisy time traces.

Antoine Ferrein (1693-1769)-His Life and Contribution to Anatomy and Physiology: The Description of the Vocal Chords and Their Function.

The purpose of this study is to summarize the life and work of the French anatomist and surgeon Antoine Ferrein (1693-1769). Ferrein made an impact in the history of anatomy and physiology through his work and especially with the description of phonation, renal anatomy, and liver and biliary structure. He also made an impact on ophthalmology with the description of the eyelid and its diseases. After a thorough review of the literature, we present in this review his life and his main discoveries with special emphasis on the anatomic description of the vocal chords resembling the chords of a violin tempered by the air exhaled from the lungs and how the physiology of phonation and the surgery of the larynx were revolutionized after that.

Quantitative Mapping of Endosomal DNA Processing by Single Molecule Counting.

Extracellular DNA is engulfed by innate immune cells and digested by endosomal DNase II to generate an immune response. Quantitative information on endosomal stage-specific cargo processing is a critical parameter to predict and model the innate immune response. Biochemical assays quantify endosomal processing but lack organelle-specific information, while fluorescence microscopy has provided the latter without the former. Herein, we report a single molecule counting method based on fluorescence imaging that quantitatively maps endosomal processing of cargo DNA in innate immune cells with organelle-specific resolution. Our studies reveal that endosomal DNA degradation occurs mainly in lysosomes and is negligible in late endosomes. This method can be used to study cargo processing in diverse endocytic pathways and measure stage-specific activity of processing factors in endosomes.

Primary and secondary hyperparathyroidism among vitamin D deficient Hashimoto's thyroiditis patients and the need for a parathyroid scan.

The patients with Hashimoto thyroiditis must be investigated mainly for secondary hyperparathyroidism due to vitamin D deficiency/insufficiency. Parathyroid scintigraphy has no place in the diagnosis of primary, secondary or tertiary hyperparathyroidism or in the decision for surgical treatment. Parathyroid scintigraphy is a useful preoperative technique for the localization of the pathological parathyroid glands.

Unraveling the Thousand Word Picture: An Introduction to Super-Resolution Data Analysis.

Super-resolution microscopy provides direct insight into fundamental biological processes occurring at length scales smaller than light's diffraction limit. The analysis of data at such scales has brought statistical and machine learning methods into the mainstream. Here we provide a survey of data analysis methods starting from an overview of basic statistical techniques underlying the analysis of super-resolution and, more broadly, imaging data. We subsequently break down the analysis of super-resolution data into four problems: the localization problem, the counting problem, the linking problem, and what we've termed the interpretation problem.

Hydrodynamic Hunters.

The Gram-negative Bdellovibrio bacteriovorus (BV) is a model bacterial predator that hunts other bacteria and may serve as a living antibiotic. Despite over 50 years since its discovery, it is suggested that BV probably collides into its prey at random. It remains unclear to what degree, if any, BV uses chemical cues to target its prey. The targeted search problem by the predator for its prey in three dimensions is a difficult problem: it requires the predator to sensitively detect prey and forecast its mobile prey's future position on the basis of previously detected signal. Here instead we find that rather than chemically detecting prey, hydrodynamics forces BV into regions high in prey density, thereby improving its odds of a chance collision with prey and ultimately reducing BV's search space for prey. We do so by showing that BV's dynamics are strongly influenced by self-generated hydrodynamic flow fields forcing BV onto surfaces and, for large enough defects on surfaces, forcing BV in orbital motion around these defects. Key experimental controls and calculations recapitulate the hydrodynamic origin of these behaviors. While BV's prey (Escherichia coli) are too small to trap BV in hydrodynamic orbit, the prey are also susceptible to their own hydrodynamic fields, substantially confining them to surfaces and defects where mobile predator and prey density is now dramatically enhanced. Colocalization, driven by hydrodynamics, ultimately reduces BV's search space for prey from three to two dimensions (on surfaces) even down to a single dimension (around defects). We conclude that BV's search for individual prey remains random, as suggested in the literature, but confined, however-by generic hydrodynamic forces-to reduced dimensionality.

A novel method to accurately locate and count large numbers of steps by photobleaching.

Photobleaching event counting is a single-molecule fluorescence technique that is increasingly being used to determine the stoichiometry of protein and RNA complexes composed of many subunits in vivo as well as in vitro. By tagging protein or RNA subunits with fluorophores, activating them, and subsequently observing as the fluorophores photobleach, one obtains information on the number of subunits in a complex. The noise properties in a photobleaching time trace depend on the number of active fluorescent subunits. Thus, as fluorophores stochastically photobleach, noise properties of the time trace change stochastically, and these varying noise properties have created a challenge in identifying photobleaching steps in a time trace. Although photobleaching steps are often detected by eye, this method only works for high individual fluorophore emission signal-to-noise ratios and small numbers of fluorophores. With filtering methods or currently available algorithms, it is possible to reliably identify photobleaching steps for up to 20-30 fluorophores and signal-to-noise ratios down to ∼1. Here we present a new Bayesian method of counting steps in photobleaching time traces that takes into account stochastic noise variation in addition to complications such as overlapping photobleaching events that may arise from fluorophore interactions, as well as on-off blinking. Our method is capable of detecting ≥50 photobleaching steps even for signal-to-noise ratios as low as 0.1, can find up to ≥500 steps for more favorable noise profiles, and is computationally inexpensive.

Is vitamin D related to pathogenesis and treatment of Hashimoto's thyroiditis?

OBJECTIVE: The aim of this study was to investigate vitamin D status by measuring serum 25(OH)D levels in euthyroid patients with Hashimoto's thyroiditis (HT) who lived and worked on the sunny island of Crete, Greece, and to evaluate whether vitamin D3 supplementation is beneficial for the management of HT patients with vitamin D deficiency. SUBJECTS AND METHODS: We studied 218 HT patients, euthyroid Caucasian Cretan Greek citizens: 180 females and 38 males. Among these patients, 186 (85.3%) had vitamin D deficiency defined as serum 25(OH)D levels < 30 ng/mL. The mean age of all these 218 HT patients was 35.3 ± 8.5 years. The mean age of the 186 vitamin D deficient HT patients (173 females and 13 males) was 37.3 ± 5.6 years. The 186 vitamin D deficient HT patients received vitamin D3 (cholecalciferol, CF) orally, 1200-4000 IU, every day for 4 months aiming to maintain serum 25(OH)D levels ≥ 40 ng/mL. Anthropometric characteristics (height, weight, waist circumference), systolic and diastolic blood pressure, serum concentration of 25(OH)D, thyrotropin (TSH), free thyroxine (FT4), anti-thyroid peroxidase (anti-TPO), antithyroglobulin (anti-TG), calcium and phosphorus levels and thyroid and kidney sonographic findings were recorded and measured before and after CF administration. RESULTS: There was a significant negative correlation only between serum 25(OH)D levels and anti-TPO levels among all 218 HT patients. Also, anti-TPO levels were significantly higher in 186/218 vitamin D deficient HT patients compared to 32/218 HT patients with no vitamin D deficiency (364 ± 181IU/mL versus 115.8 ± 37.1IU/mL, P<0.0001). Supplementation of CF in 186 vitamin D deficient HT patients caused a significant decrease (20.3%) in serum anti-TPO levels. Although at the end of the 4 months period of the study body mass index (BMI), serum anti-TG and TSH levels decreased by 2.2%, 5.3% and 4% respectively, these differences were not significant. No changes in the sonographic findings were observed. CONCLUSION: The majority (85.3%) of the Greek Caucasian patients with HT studied who lived and worked in Crete had low serum 25(OH)D levels inversely correlated with serum anti-TPO thyroid antibodies. After 4 months of CF supplementation in the 186 HT patients with vitamin D deficiency, a significant decrease (20.3%) of serum anti-TPO levels was found. These findings suggest that vitamin D deficiency may be related to pathogenesis of HT and that its supplementation could contribute to the treatment of patients with HT.

Inferring diffusion dynamics from FCS in heterogeneous nuclear environments.

Fluorescence correlation spectroscopy (FCS) is a noninvasive technique that probes the diffusion dynamics of proteins down to single-molecule sensitivity in living cells. Critical mechanistic insight is often drawn from FCS experiments by fitting the resulting time-intensity correlation function, G(t), to known diffusion models. When simple models fail, the complex diffusion dynamics of proteins within heterogeneous cellular environments can be fit to anomalous diffusion models with adjustable anomalous exponents. Here, we take a different approach. We use the maximum entropy method to show-first using synthetic data-that a model for proteins diffusing while stochastically binding/unbinding to various affinity sites in living cells gives rise to a G(t) that could otherwise be equally well fit using anomalous diffusion models. We explain the mechanistic insight derived from our method. In particular, using real FCS data, we describe how the effects of cell crowding and binding to affinity sites manifest themselves in the behavior of G(t). Our focus is on the diffusive behavior of an engineered protein in 1) the heterochromatin region of the cell's nucleus as well as 2) in the cell's cytoplasm and 3) in solution. The protein consists of the basic region-leucine zipper (BZip) domain of the CCAAT/enhancer-binding protein (C/EBP) fused to fluorescent proteins.

The heat released during catalytic turnover enhances the diffusion of an enzyme.

Recent studies have shown that the diffusivity of enzymes increases in a substrate-dependent manner during catalysis. Although this observation has been reported and characterized for several different systems, the precise origin of this phenomenon is unknown. Calorimetric methods are often used to determine enthalpies from enzyme-catalysed reactions and can therefore provide important insight into their reaction mechanisms. The ensemble averages involved in traditional bulk calorimetry cannot probe the transient effects that the energy exchanged in a reaction may have on the catalyst. Here we obtain single-molecule fluorescence correlation spectroscopy data and analyse them within the framework of a stochastic theory to demonstrate a mechanistic link between the enhanced diffusion of a single enzyme molecule and the heat released in the reaction. We propose that the heat released during catalysis generates an asymmetric pressure wave that results in a differential stress at the protein-solvent interface that transiently displaces the centre-of-mass of the enzyme (chemoacoustic effect). This novel perspective on how enzymes respond to the energy released during catalysis suggests a possible effect of the heat of reaction on the structural integrity and internal degrees of freedom of the enzyme.

Design of High-Specificity Nanocarriers by Exploiting Non-Equilibrium Effects in Cancer Cell Targeting.

Although targeting of cancer cells using drug-delivering nanocarriers holds promise for improving therapeutic agent specificity, the strategy of maximizing ligand affinity for receptors overexpressed on cancer cells is suboptimal. To determine design principles that maximize nanocarrier specificity for cancer cells, we studied a generalized kinetics-based theoretical model of nanocarriers with one or more ligands that specifically bind these overexpressed receptors. We show that kinetics inherent to the system play an important role in determining specificity and can in fact be exploited to attain orders of magnitude improvement in specificity. In contrast to the current trend of therapeutic design, we show that these specificity increases can generally be achieved by a combination of low rates of endocytosis and nanocarriers with multiple low-affinity ligands. These results are broadly robust across endocytosis mechanisms and drug-delivery protocols, suggesting the need for a paradigm shift in receptor-targeted drug-delivery design.

White matter and deep gray matter hemodynamic changes in multiple sclerosis patients with clinically isolated syndrome.

The dynamic susceptibility contrast magnetic resonance imaging perfusion technique was used to investigate possible hemodynamic changes in normal appearing white matter and deep gray matter (DGM) of 30 patients with clinically isolated syndrome (CIS) and 30 patients with relapsing-remitting multiple sclerosis. Thirty normal volunteers were studied as controls. Cerebral blood volume, cerebral blood flow (CBF), and mean transit time values were estimated. Normalization was achieved for each subject with respect to average values of CBF and mean transit time of the hippocampi's dentate gyrus. Measurements concerned three regions of normal white matter of normal volunteers, normal appearing white matter of CIS and patients with relapsing-remitting multiple sclerosis, and DGM regions, bilaterally. All measured normal appearing white matter and DGM regions of the patients with CIS had significantly higher cerebral blood volume and mean transit time values, while averaged DGM regions had significantly lower CBF values, compared to those of normal volunteers (P < 0.001). Regarding patients with relapsing-remitting multiple sclerosis, all measured normal appearing white matter and DGM regions showed lower CBF values than those of normal volunteers and lower cerebral blood volume and CBF values compared to patients with CIS (P < 0.001). These data provide strong evidence that hemodynamic changes--affecting both white and DGM--may occur even at the earliest stage of multiple sclerosis, with CIS patients being significantly different than relapsing-remitting multiple sclerosis patients.