peri-Adventitial delivery of smooth muscle cells in porous collagen scaffolds for treatment of experimental abdominal aortic aneurysm.
Abdominal aortic aneurysm (AAA) is associated with the loss of vascular smooth muscle cells (SMCs) within the vessel wall. Direct delivery of therapeutic cells is challenging due to impaired mechanical integrity of the vessel wall. We hypothesized that porous collagen scaffolds can be an effective vehicle for the delivery of human-derived SMCs to the site of AAA. The purpose was to evaluate if the delivery of cell-seeded scaffolds can abrogate progressive expansion in a mouse model of AAA. Collagen scaffolds seeded with either primary human aortic SMCs or induced pluripotent stem cell derived-smooth muscle progenitor cells (iPSC-SMPs) had >80% in vitro cell viability and >75% cell penetrance through the scaffold's depth, while preserving smooth muscle phenotype. The cell-seeded scaffolds were successfully transplanted onto the murine aneurysm peri-adventitia on day 7 following AAA induction using pancreatic porcine elastase infusion. Ultrasound imaging revealed that SMC-seeded scaffolds significantly reduced the aortic diameter by 28 days, compared to scaffolds seeded with iPSC-SMPs or without cells (acellular scaffold), respectively. Bioluminescence imaging demonstrated that both cell-seeded scaffold groups had cellular localization to the aneurysm but a decline in survival with time. Histological analysis revealed that both cell-seeded scaffold groups had more SMC retention and less macrophage invasion into the medial layer of AAA lesions, when compared to the acellular scaffold treatment group. Our data suggest that scaffold-based SMC delivery is feasible and may constitute a platform for cell-based AAA therapy.


Processing treatments for mitigating acrylamide formation in sweetpotato French fries.
Acrylamide formation in sweetpotato French fries (SPFF) is likely a potential health concern as there is an increasing demand for good-quality fries from carotene-rich sweetpotatoes (SP). This is the first report on acrylamide formation in SPFF as affected by processing methods. Acrylamide levels in SPFF from untreated SP strips fried at 165 °C for 2, 3, and 5 min were 124.9, 255.5, and 452.0 ng/g fresh weight, which were reduced by about 7 times to 16.3, 36.9, and 58.3 ng/g, respectively, when the strips were subjected to processing that included water blanching and soaking in 0.5% sodium acid pyrophosphate before frying. An additional step of strip soaking in 0.4% calcium chloride solution before par-frying increased the calcium content from 0.2 to 0.8 mg/g and decreased the acrylamide levels to 6.3, 17.6, and 35.4 ng/g, respectively. SPFF with acrylamide level of <100 ng/g or several times lower than that of white potato French fries can be obtained by integrating processing treatments commonly used in the food industry.


[Diagnosis and management of tenosynovial giant cell tumor].
Tenosynovial giant cell tumor is a benign condition that originates from synovial cells within joints, tendon sheaths, or bursae and may present either in localized (benign) or diffuse (locally aggressive) forms. Currently, the primary treatment approach is surgical, yielding satisfactory results with low recurrence rates in the localized forms, whereas the diffuse type displays high recurrence rates. In parallel, clinical trials are underway to explore pharmaceutical treatment options for the advanced diffuse type. This article aims at consolidating current knowledge about diagnosis and management of this rare tumor, additionally proposing a brief overview of novel therapeutic approaches.


Inhibition of return and the attentional set for integrating versus differentiating information.
Cuing a location with an uninformative cue leads to a facilitatory effect at that location shortly afterward and later (about 300 ms) to a negative effect called inhibition of return (IOR). Until recently, it was argued that IOR occurs in detection and localization tasks, but not in discrimination tasks. However, the authors of several recent studies have demonstrated IOR effects in discrimination tasks, although at a later cue-to-target stimulus onset asynchrony (SOA). In this study, the authors examined why IOR occurs at a later SOA in discrimination tasks. In Experiments 1 and 2, different time courses of exogenous cuing effects in detection and discrimination tasks were established. In Experiment 3, the authors examined the role of an attentional set on the time course of exogenous cuing effects by manipulating the proportion of trials in which a distractor is presented in the location opposite the target. A new framework for understanding exogenous cuing effects and their dependence on endogenous attention is proposed.


Antigenicity and immunogenicity of synthetic peptides of foot-and-mouth disease virus.
Peptides reactive with two neutralizing monoclonal antibodies raised against intact foot-and-mouth disease virus A10 were identified with the aid of all overlapping (hexa)peptides of the outer structural viral protein VP1 and located on the viral surface. Using this procedure, it was possible to define those amino acids within a peptide which were critical in the binding of antibody to that peptide. One eight amino acid long peptide, containing six such amino acids, was virtually indistinguishable from viral antigen in its ability to bind monoclonal antibody as determined by competition tests. Another peptide, which was able to induce neutralizing activity as well, showed no competition and possessed fewer amino acids contributing to binding. This peptide appeared to be an incomplete epitope. Comparison of our data with those of others suggests that this may apply commonly to the reactive peptides described.


POU4F3 mutation screening in Japanese hearing loss patients: Massively parallel DNA sequencing-based analysis identified novel variants associated with autosomal dominant hearing loss.
A variant in a transcription factor gene, POU4F3, is responsible for autosomal dominant nonsyndromic hereditary hearing loss, DFNA15. To date, 14 variants, including a whole deletion of POU4F3, have been reported to cause HL in various ethnic groups. In the present study, genetic screening for POU4F3 variants was carried out for a large series of Japanese hearing loss (HL) patients to clarify the prevalence and clinical characteristics of DFNA15 in the Japanese population. Massively parallel DNA sequencing of 68 target candidate genes was utilized in 2,549 unrelated Japanese HL patients (probands) to identify genomic variations responsible for HL. The detailed clinical features in patients with POU4F3 variants were collected from medical charts and analyzed. Novel 12 POU4F3 likely pathogenic variants (six missense variants, three frameshift variants, and three nonsense variants) were successfully identified in 15 probands (2.5%) among 602 families exhibiting autosomal dominant HL, whereas no variants were detected in the other 1,947 probands with autosomal recessive or inheritance pattern unknown HL. To obtain the audiovestibular configuration of the patients harboring POU4F3 variants, we collected audiograms and vestibular symptoms of the probands and their affected family members. Audiovestibular phenotypes in a total of 24 individuals from the 15 families possessing variants were characterized by progressive HL, with a large variation in the onset age and severity with or without vestibular symptoms observed. Pure-tone audiograms indicated the most prevalent configuration as mid-frequency HL type followed by high-frequency HL type, with asymmetry observed in approximately 20% of affected individuals. Analysis of the relationship between age and pure-tone average suggested that individuals with truncating variants showed earlier onset and slower progression of HL than did those with non-truncating variants. The present study showed that variants in POU4F3 were a common cause of autosomal dominant HL.


Interactions of amphotericin B and SCH 39304 in the treatment of experimental murine candidiasis: lack of antagonism of a polyene-azole combination.
Mice infected intravenously with Candida albicans were treated with SCH 39304, a new triazole antifungal compound, amphotericin B, or both. Two dose levels of each drug were evaluated in an attempt to identify potential helpful or harmful effects on survival and kidney colony counts. Contrary to theoretical predictions, combination therapy was not antagonistic and some additive or synergistic effects were observed. The results obtained in this study suggest that antagonism between polyene and azole antifungal drugs is not inevitable and that additive or synergistic effects may be possible.


Extrathymic hemopoietic progenitors committed to T cell differentiation in the adult mouse.
The role of the thymus in T cell commitment of hemopoietic precursor is yet controversial. We previously identified a major T cell progenitor activity in precursor cells isolated from bone marrow-derived spleen colonies. In this study, we characterize the properties of these pre-T cells. We demonstrate that they have unique phenotype and can be generated in a total absence of any thymic influence. Indeed, even when studied at the single-cell level, extrathymic T cell-committed precursors express T cell-specific genes. Moreover, these cells are not committed to a particular T cell differentiation pathway because they can generate both extrathymic CD8alphaalpha+ intraepithelial lymphocytes and thymus-derived conventional thymocytes. We also compared these pre-T cells with fully T cell-committed thymic progenitors. When tested in vitro or by direct intrathymic transfer, these cells have a low clonogenic activity. However, after i.v. transfer, thymus repopulation is efficient and these precursors generate very high numbers of peripheral T cells. These results suggest the existence of extra steps of pre-T cell maturation that improve thymus reconstitution capacity and that can be delivered even after full T cell commitment. Consequently, our studies identify a source of extrathymic progenitors that will be helpful in defining the role of the thymus in the earliest steps of T cell differentiation.


Nuclear magnetic relaxation dispersion of murine tissue for development of T1 (R1 ) dispersion contrast imaging.
This study quantified the spin-lattice relaxation rate (R1 ) dispersion of murine tissues from 0.24 mT to 3 T. A combination of ex vivo and in vivo spin-lattice relaxation rate measurements were acquired for murine tissue. Selected brain, liver, kidney, muscle, and fat tissues were excised and R1 dispersion profiles were acquired from 0.24 mT to 1.0 T at 37 °C, using a fast field-cycling MR (FFC-MR) relaxometer. In vivo R1 dispersion profiles of mice were acquired from 1.26 T to 1.74 T at 37 °C, using FFC-MRI on a 1.5 T scanner outfitted with a field-cycling insert electromagnet to dynamically control B0 prior to imaging. Images at five field strengths (1.26, 1.39, 1.5, 1.61, 1.74 T) were acquired using a field-cycling pulse sequence, where B0 was modulated for varying relaxation durations prior to imaging. R1 maps and R1 dispersion (ΔR1 /ΔB0 ) were calculated at 1.5 T on a pixel-by-pixel basis. In addition, in vivo R1 maps of mice were acquired at 3 T. At fields less than 1 T, a large R1 magnetic field dependence was observed for tissues. ROI analysis of the tissues showed little relaxation dispersion for magnetic fields from 1.26 T to 3 T. Our tissue measurements show strong R1 dispersion at field strengths less than 1 T and limited R1 dispersion at field strengths greater than 1 T. These findings emphasize the inherent weak R1 magnetic field dependence of healthy tissues at clinical field strengths. This characteristic of tissues can be exploited by a combination of FFC-MRI and T1 contrast agents that exhibit strong relaxivity magnetic field dependences (inherent or by binding to a protein), thereby increasing the agents' specificity and sensitivity. This development can provide potential insights into protein-based biomarkers using FFC-MRI to assess early changes in tumour development, which are not easily measureable with conventional MRI.


Triplex formation by a psoralen-conjugated oligodeoxyribonucleotide containing the base analog 8-oxo-adenine.
Oligodeoxyribonucleotides containing thymidine and 8-oxo-2'-deoxyadenosine can form pyr.pur.pyr type triplexes with double-stranded DNA. Unlike triplexes whose third strands contain thymidine and deoxycytidine, the stability of these triplexes is independent of pH. We have prepared d-ps-TAAATAAATTTTTAT-L [I(A)], where A is 8-oxo-2'-deoxyadenosine, ps is 4'-hydroxymethyl-4,5',8- trimethylpsoralen and L is a 6-amino-2-(hydroxymethyl)hexyl linker. The oligomer is designed to interact with a homopurine sequence in the promoter region of the human gene coding for the 92 kDa form of collagenase type IV. Oligomer I(A) and oligomer I(C), which contains 2'-deoxycytidine in place of 8-oxo-2'-deoxycytidine, both form stable triplexes at pH 6.2, but only I(A) forms a stable triplex with a model duplex DNA target at pH 7.5, as determined by UV melting experiments. Triplex formation is stabilized by the presence of the psoralen group. Upon irradiation both I(A) and I(C) form photoadducts with the DNA target at pH 6.2, but only I(A) forms a photoadduct at pH 7.5. In these photoreactions oligomer I(A) appears to selectively form a photoadduct with a C in the purine-rich strand of the duplex target. Although a T residue is present in the pyrimidine-rich strand of the target at the duplex/triplex junction, essentially no adduct formation takes place with this strand, nor is interstrand cross-linking observed. The extent of photoadduct formation decreases with increasing temperature, behavior which is consistent with the UV melting curve of the triplex. A tetramethylrhodamine derivative of I(A) was prepared and found to cross-link less extensively than I(A) itself. Oligomer I(A) is completely resistant to hydrolysis when incubated for 24h in the presence of 10% fetal bovine serum at 37 degree C, although it is hydrolyzed by S1 nuclease. The properties of oligomer I(A) suggest that 8-oxo- containing oligomers may find utility as antigene oligonucleotide reagents.


Conference report for the 10th China Bioanalysis Forum annual meeting.
The 10th China Bioanalysis Forum annual conference was held in Suzhou between 9 and 11 June 2023. This year a full range of bioanalytical topics were discussed such as new technology and bioanalytical approaches for biotherapeutics and biomarkers, particularly in the areas of gene and cell therapy. Another research area covered extensively at the conference was drug metabolism, including new drug metabolism and pharmacokinetic methods; absorption, distribution, metabolism and excretion of new modality drugs, recent regulatory guidance such as human mass balance study and preclinical study of antibody-drug conjugates and case studies of drug metabolism support to newly approved drugs.


A stability indicating HPLC method for determination of mebeverine in the presence of its degradation products and kinetic study of its degradation in oxidative condition.
An HPLC method for determination of mebeverine hydrochloride (MH) in the presence of its degradation products was developed. The degradation of MH was studied under hydrolysis, oxidative and photolysis stress conditions. Under alkaline, acidic and oxidative conditions, degradation of MH was observed. The separation was performed using a Symmetry C18 column and a mixture of 50 mM KH2PO4, acetonitrile and tetrahydrfuran (THF) (63:35:2; v/v/v) as the mobile phase. No interference peaks from degradation products in acidic, alkaline and oxidative conditions were observed. The linearity, accuracy and precision of the method were studied. The method was linear over the range of 1-100 μg/ml MH (r(2)>0.999) and the CV values for intra-day and inter-day variations were in the range of 1.0-1.8%. The limit of quantification (LOQ) and the limit of detection (LOD) of the method were 1.0 and 0.2 μg/ml, respectively. Determination of MH in pharmaceutical dosage forms was performed using the developed method. Furthermore the kinetics of the degradation of MH in the presence of hydrogen peroxide was investigated. The proposed method could be a suitable method for routine quality control studies of mebeverine dosage forms.


Traditionalism and its relationship to disease risk and protective behaviors of women living on the Hopi reservation.
The fundamental aim of this study was to identify factors crucial for the development of effective cancer prevention programs for American Indian (AI) populations. Toward that end, we developed an instrument to assess the influence of traditionalism on health risks such as smoking, consumption, and obesity. A population-based survey was conducted among 559 randomly selected women living on the Hopi reservation aged 18 years and older, from July through December 1993. To construct a traditionalism score, we conducted focus groups in the community. A multidimensional approach was adopted by assessing three dimensions of native culture: language usage; cultural participation, or participation in such activities as Hopi ceremonies; and percentage of life spent off-reservation. A mean score of the three dimensions was computed for each respondent. High levels of traditionalism were significantly associated with disease protective behaviors, such as practicing traditional Hopi activities to keep healthy (OR = 3.07), and significantly inversely associated with disease risk factors such as smoking (OR = 0.26) and obesity (OR = 0.60) independent of age, marital status, and education. As these data provide a strong rationale for the promotion of traditions in public health programs aimed at decreasing rates of chronic disease among AI women, we conclude this paper with a discussion of the importance of traditionalism and how it might be accurately assessed.


Toward Martian agriculture: responses of plants to hypobaria.
The recent surge of interest in human missions to Mars has also generated considerable interest in the responses of plants to hypobaria (reduced atmospheric pressure), particularly among those in the advanced life support community. Potential for in situ resource utilization, challenges in meeting engineering constraints for mass and energy, the prospect of using lightweight plant growth structures on Mars, and the minimal literature on plant responses to low pressure all suggest much needed research in this area. However, the limited literature on hypobaria combined with previous findings on plant responses to atmospheric composition and established principles of mass transfer of gases suggest that some plants will be capable of tolerating and growing at pressures below 20 kPa; and for other species, perhaps as low as 5-10 kPa. In addition, normal and perhaps enhanced growth of many plants will likely occur at reduced partial pressures of oxygen (e.g., 5 kPa). Growth of plants at such low and partial pressures indicates the feasibility of cultivating plants in lightweight, transparent "greenhouses" on the surface of Mars or in other extraterrestrial or extreme environment locations. There are numerous, accessible terrestrial analogs for moderately low pressure ranges, but not for very low and extremely low atmospheric pressures. Research pertaining to very low pressures has been historically restricted to the use of vacuum chambers. Future research prospects, approaches, and priorities for plant growth experiments at low pressure are considered and discussed as they apply to prospects for Martian agriculture.


Multilevel intervention for prevention of fetal alcohol syndrome and effects of prenatal alcohol exposure.
The deleterious effects of prenatal alcohol exposure have been the subject of numerous research studies since first recognized in the early 1970s. The results of these studies have indicated that the dose and patterning of maternal alcohol consumption, use of other drugs, as well as other social and environmental factors may mediate developmental outcomes in prenatally alcohol-exposed children. Although there are still many unanswered questions regarding etiology, there is a clearly identified need for effective prevention/intervention programs for alcohol-abusing women of childbearing age. Such programs must address the multiple factors that may exacerbate alcohol's teratogenic effects. The prevention of fetal alcohol syndrome (FAS) and other alcohol-related birth defects (ARBD) can only be accomplished through multilevel, multisystem intervention strategies, including community education, therapeutic interventions with the alcohol-abusing mother, parenting education, and early identification and intervention with the alcohol-affected child. A review on the etiology of FAS and ARBD is presented with recommended strategies for prevention/intervention.


Lifestyle, dietary, and medical history factors associated with pancreatic cancer risk in Ontario, Canada.
Pancreatic adenocarcinoma has one of the worst survival rates of all the cancers. Established risk factors for this malignancy are smoking, body mass index (BMI) and family history of pancreatic cancer. Findings are inconsistent regarding pancreatitis, diabetes, allergies, intake of fruit, vegetables, red meat, alcohol, caffeine, vitamin C, calcium, and folate supplements. Possible pancreatic cancer risk factors were evaluated within the population-based Ontario Pancreas Cancer Study. Pathologically confirmed pancreatic cancer cases (n = 422) were identified from the Ontario Cancer Registry between 2003 and 2007. Controls (n = 312) were recruited through random digit dialing. Data were collected using self-administered questionnaires. Multivariate logistic regression was used to obtain odds ratios. Smoking, BMI, family history of pancreatic cancer, and caffeine were significantly associated with increased pancreatic cancer risk, while fruit intake and allergies significantly decreased risk. No other significant associations were observed in the multivariate model. Effect modification by smoking status was suggested for caffeine, family history of pancreatic cancer, BMI, and fruit. This study further clarifies the association between several lifestyle, dietary and medical history factors, and pancreatic cancer risk, many of which are potentially modifiable. Possible effect modification by smoking status should be further explored in future etiologic studies.


Characteristics and post-metastasis survival of recurrent metastatic breast cancer over time - An Australian population-based record linkage study, 2001-2016.
To assess population-level characteristics and post-metastasis survival of people with recurrent metastatic breast cancer (rMBC) during a period when new publicly-subsidised adjuvant and metastatic systemic therapies became available. Record linkage study of females in NSW Cancer Registry (NSWCR) diagnosed with non-metastatic breast cancer (BC) in 2001-2002 (C1) and 2006-2007 (C2). We identified first rMBC from NSWCR, administrative hospital records, dispensed medicines and radiotherapy services (2001-2016). We used death registrations to estimate cumulative incidence of BC death. The analysis included 2267 women with rMBC (C1:1210, C2:1057). Compared to C1, C2 had access to adjuvant HER2-targeted therapy and were more likely to have received adjuvant chemotherapy (C1:38%, C2:47%) and aromatase inhibitors (C1:52%, C2:73%, of those dispensed endocrine therapy). Five-year probability of BC death was 65% (95%CI:62-68%) in C1 and 63% (95%CI:60-66%) in C2. Regional disease (T4 or N + ) at initial BC diagnosis (C1:62%, C2:68%), and age ≥ 70 years at first metastasis (C1:27%, C2:31%) were more common in C2 and had poorer prognosis. Five-year probability of BC death was lower in C2 than C1 for treatment-defined HER2-positive BC (C1:72% 95%CI:63-79%; C2:52% 95%CI 45-60%) and those dispensed chemotherapy alone (C1:76% 95%CI:69-82, C2:67% 95%CI:59-74%, p = 0.01), but not treatment-defined hormone receptor-positive HER2-negative BC (C1:60% 95%CI 56-63%, C2:64% 95%CI 60-68%). Despite less favourable prognostic characteristics in C2, BC-related survival following rMBC was similar between the two cohorts; and improved for women with HER2-positive tumours. These findings support the real-world benefits of newer treatments for rMBC.


Age-related changes in renal function, membrane protein metabolism, and Na,K-ATPase activity and abundance in hypokalemic F344 x BNF(1) rats.
Potassium depletion is a common electrolyte abnormality in elderly humans, usually as a consequence of diuretic use or poor oral intake. Hypokalemia is associated with a number of changes in renal function and an increase in some renal membrane transporters; its growth-promoting effect in young animals is well known. With aging, the renal adaptation to a number of challenges is often diminished. We hypothesized that aging is related to decreases in renal function, renal membrane protein metabolism, as well as Na, K-ATPase protein abundance and activity in both control animals as well as in those with potassium depletion. We examined the effects of dietary-induced hypokalemia in true-aged nonobese rats (30 months old) on renal function, cortical brush border membrane (BBM) and basolateral membrane (BLM) protein metabolism, and Na,K-ATPase protein abundance and activity. We compared the results obtained to those seen in their 4-month-old counterparts similarly treated. Young (4-month-old) and senescent (30-month-old) male Fisher 344 x Brown-Norway F(1) rats (F344 x BNF(1)) were fed either a normal or potassium-deficient diet for 7 days. At 24 h, the U-(14)C-leucine incorporation was measured for determination of protein metabolism in renal BBM and BLM. Cortical BLM vesicle and microdissected proximal convoluted tubule (PCT) Na, K-ATPase activities were determined along with Western blot analysis of the cortical BLM alpha(1) subunit of Na,K-ATPase. Metabolic and renal function parameters were also examined. Hypokalemia caused hyperbicarbonatemia, hyperglycemia, and azotemia, but only in the senescent animals. The aged control rats had a higher basal level of urine volume, ammonium excretion, and fractional excretion of chloride. By contrast, aging in the F344 x BNF(1) rats was associated with a decrease in plasma aldosterone (by 35%) and phosphate (by 40%) levels as compared with their young controls. Hypokalemia resulted in a significant reduction of plasma aldosterone and a rise in muscle sodium concentration in both age groups; it significantly increased renal BBM and BLM protein concentrations in the young group, while these parameters remained unchanged in the senescent rats. The aged potassium-depleted animals showed a 14% decrease in BBM protein biosynthesis, but there were no changes in the young hypokalemic rats. Both potassium-depleted elderly and young rats had a significant reduction (by 33%) in BLM protein biosynthesis. Hypokalemia significantly increased the Na, K-ATPase activity in both cortical BLM vesicles and in microdissected PCT. The percentage increase in microdissected PCT segments (Na,K-ATPase activity) in elderly potassium-depleted animals was significantly less than that seen in hypokalemic young ones. Aging, per se, was associated with decreased basal microdissected PCT Na,K-ATPase activity in control animals. Hypokalemia had no effect on cortical BLM alpha(1) subunit Na, K-ATPase protein abundance in either age group. The present study provides the first evidence in nonobese aged rats as to the metabolic parameters, renal function, renal cortical membrane protein metabolism, and transporter Na,K-ATPase activity and abundance during potassium depletion. The aged nonobese F344 x BNF(1) rats responded differently from their young nonobese counterparts following potassium depletion. These differences may contribute substantially to the effects often encountered in elderly humans receiving diuretics or having a poor dietary potassium intake.


[Paraneoplastic hyperthyroidism in a patient with metastasizing teratocarcinoma and excessively high HCG].
Clinically manifest hyperthyroidism is a rare paraneoplastic syndrome in patients with excessive HCG production due to testicular cancer. A 40-year-old patient with right testicular cancer (teratoma, embryonal cell carcinoma), diffuse pulmonary metastases and high serum HCG levels presented with symptomatic hyperthyroidism. The patient received immediately thyrostatic therapy and 4 cycles of PEI chemotherapy (Cisplatin, Etoposide, Ifosfamide). Thyroid function had returned to normal by the beginning of the second course of chemotherapy. After right orchiectomy and resection of residual pulmonary masses which revealed vital tumor cells, two additional courses of chemotherapy were performed. The patient is well and without evidence of disease 11 months after therapy. All patients with testicular cancer and excessive HCG production should be evaluated for biochemical and clinical signs of hyperthyroidism and treated accordingly with antithyroidal medication and immediate cytoreductive chemotherapy.


Titration of basal insulin or immediate addition of rapid acting insulin in patients not at target using basal insulin supported oral antidiabetic treatment - A prospective observational study in 2202 patients.
Optimal treatment intensification strategies in patients with type-2 diabetes mellitus (T2DM) receiving basal insulin supported oral antidiabetic therapy (BOT) remain controversial. The objective of the present study was to compare outcomes of BOT-intensification by either the uptitration of long-acting insulin glargine or by the immediate addition of a rapid acting insulin analogue (RAIA). This was a prospective, observational, 24-week study in T2DM patients with BOT using insulin glargine and baseline glycated hemoglobin (HbA1c) between 7.0 and 8.5%. Patients were stratified by their physicians to one of the following treatment intensification strategies: Basal insulin titration to target with discretionary subsequent addition of RAIA at weeks 12 or 24 (GLAR), or immediate addition of RAIA at baseline (GLARplus). A total of 3266 patients were prescreened of whom 2202 fulfilled the selection criteria. Of these, 1684 patients were documented in the GLAR group and 518 in the GLARplus group. In the GLAR group, in 91 (5.5%) and 21 patients (1.3%) RAIA was added at weeks 12 and 24, respectively. The groups displayed similar baseline characteristics; except, mean diabetes duration was slightly shorter in the GLAR group (8.7 vs. 9.4 years). During the study, insulin glargine dose was increased from 18.7 to 26.4U (plus 7.7U) in GLAR and from 24.9 to 27.3U (plus 2.4U) in GLARplus patients. Mean RAIA dose was 9.6±4.7U at the final visit. After 24 weeks, HbA1c was reduced by 0.8 and 0.9% in the GLAR and GLARplus groups, respectively (both p<0.001). An HbA1c of ≤7.0% was achieved in 49.2% of GLAR and 48.5% of GLARplus patients. In both groups, we observed improvements in cardiovascular risk factors such as lipids and blood pressure. The rates of symptomatic (1.6 vs. 1.7%) and severe (0.18 vs. 0.19%) hypoglycemic episodes were low and comparable in both groups. These findings provide evidence that treatment intensification in patients with type 2 diabetes not at glycemic target on BOT with insulin glargine is equally safe and effective using either long-acting insulin titration alone or the addition of a rapid-acting insulin analogue.


Impact of climate change on parasite infection of an important pollinator depends on host genotypes.
Climate change is predicted to affect host-parasite interactions, and for some hosts, parasite infection is expected to increase with rising temperatures. Global population declines of important pollinators already have been attributed to climate change and parasitism. However, the role of climate in driving parasite infection and the genetic basis for pollinator hosts to respond often remain obscure. Based on decade-long field data, we investigated the association between climate and Nosema bombi (Microsporidia) infection of buffed-tailed bumblebees (Bombus terrestris), and whether host genotypes play a role. For this, we genotyped 876 wild bumblebee queens and screened for N. bombi infection of those queens between 2000 and 2010. We recorded seven climate parameters during those 11 years and tested for correlations between climate and infection prevalence. Here we show that climatic factors drive N. bombi infection and that the impact of climate depends on mitochondrial DNA cytochrome oxidase I (COI) haplotypes of the host. Infection prevalence was correlated with climatic variables during the time when queens emerge from hibernation. Remarkably, COI haplotypes best predict this association between climatic factors and infection. In particular, two host haplotypes ("A" and "B") displayed phenotypic plasticity in response to climatic variation: Temperature was positively correlated with infection of host haplotype B, but not haplotype A. The likelihood of infection of haplotype A was associated with moisture, conferring greater resistance to parasite infection during wetter years. In contrast, infection of haplotype B was unrelated to moisture. To the best of our knowledge, this is the first study that identifies specific host genotypes that confer differential parasite resistance under variable climatic conditions. Our results underscore the importance of mitochondrial haplotypes to ward off parasites in a changing climate. More broadly, this also suggests that COI may play a pertinent role in climate change adaptations of insect pollinators.


Is acupuncture safe in the ICU? A systematic review and meta-analysis.
The safety of interventions for critically ill patients is a crucial issue. In recent years, several studies have treated critically ill patients with acupuncture. However, the safety of acupuncture in this setting remains to be systematically measured. In May 2022, the electronic databases of PubMed and the Cochrane Library were searched for studies comparing acupuncture interventions to control interventions in critically ill patients. Study outcomes examined the incidence of severe adverse events (AEs), minor AEs, adverse reactions, ICU stays, and 28-day mortality. A total of 31 articles were analyzed, and no serious AEs related to acupuncture treatment were identified. No significant differences were found between the groups in the meta-analysis of minor AEs (risk ratio [RR] 5.69 [0.34, 96.60], P = 0.23, I2 = 76%). A reduced risk in the incidence of adverse reactions following acupuncture intervention was evidenced (RR 0.33 [0.22, 0.50], P = 0.00001, I2 = 44%). The patients in the acupuncture arm spent significantly less time in the intensive care unit (ICU) (Mean difference -1.45 [-11.94, -10.97], P = 0.00001, I2 = 56%) and also exhibited lower 28-day mortality rates (odds ratio 0.61 [0.48, 0.78], P = 0.0001, I2 = 0%). There is no evidence to indicate a higher risk of severe or minor AEs in patients who receive acupuncture. Acupuncture demonstrated favorable results in both ICU stay and 28-day mortality measurements, in addition to presenting with fewer adverse reactions compared to routine ICU care. However, the low certainty of the evidence resulting from a high risk of bias in the included studies merits substantial consideration, and further research is still warranted. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=142131, identifier: CRD42020142131.


Cultivated limbal and oral mucosal epithelial transplantation.
Stem cells located at the limbus are the ultimate source for regeneration of the corneal epithelium in normal and traumatized states. When limbal stem cells are dysfunctional or deficient, limbal stem cell deficiency (LSCD) develops. Its surgical management depends on laterality and severity of corneal-limbal involvement. Conventional methods of stem cell transplantation are conjunctival-limbal autograft (CLAU), conjunctival-limbal allograft (CLAL), and kerato-limbal allograft (KLAL) surgeries. Cultivated limbal epithelial transplantation (CLET) and cultivated oral mucosal epithelial transplantation (COMET) on a carrier such as amniotic membrane are current surgical alternatives. These new surgical procedures are effective in stabilizing the ocular surface. The theoretical advantage of ex-vivo expansions over conventional methods is that only a small limbal or mucosal biopsy is needed, thus minimizing the risk to the donor eye; there is also a lower risk of rejection. They can be used in cases with unilateral or bilateral total stem cell deficiency. In the unilateral cases, the source for CLET is a healthy fellow eye and in bilateral cases the source can be living-related or cadaveric eyes. The oral explants do not have limbal stem cells, but they seem to be a source of limbal stem cell equivalents that are able to generate cornea-like epithelium under the proper culture conditions. The main advantage of COMET is that patients with bilateral LSCD can be treated with grafts derived from their own autologous oral mucosal cells. The long-term outcomes of COMET have to be elucidated.


Breakups of an encapsulated surfactant-laden aqueous droplet under a DC electric field.
We investigate the breakups of an encapsulated conducting aqueous droplet under a direct-current electric field via extensive experiments and theoretical analysis. The encapsulating shell phase and the ambient phase consist of leaky dielectric liquids. We change the surface tension by using an aqueous core with different surfactant (Tween 80) concentrations. Moreover, we vary the core size under different electric-field conditions and observe the core dynamics. We present three different breakup modes of the encapsulated droplet. In the first mode, the encapsulated core forms asymmetric Janus shapes after breakup. In the second and third breakup modes, stable and unstable ternary droplets are formed, respectively. We show that the surfactant molecules significantly alter the dynamics of core stretching. According to the theoretical analysis, we identify the critical conditions of instability leading to breakup. We plot the breakup modes in the form of a phase diagram in the electric capillary number (Ca23 = ε3rsEo2/γ23; ratio of interfacial electric to capillary stresses) vs. radius ratio of the core to the shell (β = rc/rs) parametric space at different nondimensional surfactant concentrations (C* = CTween 80/CCMC, where CCMC represents the critical micellar concentration). The study provides essential physical insight into encapsulated emulsions and is useful for their application in various areas of science and technology.


The Remote Assessment and Dynamic Response Program: Development of an In-Home Dementia-Related Care Needs Assessment to Improve Well-Being.
The Remote Assessment and Dynamic Response (READyR) Program was developed in order to address the current lack of early-stage dementia care planning programs that assess the care needs of persons with dementia. The goal was to create a program informed by care values and ongoing ecologically valid data. The objectives of this study are to describe the development and design process of the READyR Program, and to evaluate the utility of the READyR Program for identifying dementia-related care needs. A prototype of the web-based READyR Program tool was first created using digital activity data that were collected by previous studies using a platform of multimodal sensors installed in the homes of older adult couples with and without dementia. Digital activity data were then mapped onto potential care values (e.g., safety & autonomy) to create a values-based needs assessment that is tailored to the individual care dyad. Next, evaluation of the READyR Program by 11 professional dementia care coordinators and case managers (across 3 semistructured focus groups) was used to explore the utility of READyR for assessing dementia-related needs. Qualitative description using conventional content analysis was used to iteratively code focus group data and to describe prevalent themes. Prevalent focus groups themes included barriers to (e.g., family relationship strain) and facilitators of (e.g., tailored assessments) the optimal process for assessing dementia-related care needs by care coordinators, as well as advantages to (e.g., providing new objective insights into function, and routines) and disadvantages of (e.g., bringing up new questions about care) incorporating the remote monitoring data into a values-based needs assessment. READyR has the potential to help family members, as well as care coordinators and providers, gain insight into the values-based care needs of persons with early-stage dementia. Clinical Trials Registration Number: NCT04542109.


Establishing mussel behavior as a biomarker in ecotoxicology.
Most freshwater mussel species of the Unionoida are endangered, presenting a conservation issue as they are keystone species providing essential services for aquatic ecosystems. As filter feeders with limited mobility, mussels are highly susceptible to water pollution. Despite their exposure risk, mussels are underrepresented in standard ecotoxicological methods. This study aimed to demonstrate that mussel behavioral response to a chemical stressor is a suitable biomarker for the advancement of ecotoxicology methods that aids mussel conservation. Modern software and Hall sensor technology enabled mussel filtration behavior to be monitored real-time at very high resolution. With this technology, we present our method using Anodonta anatina and record their response to de-icing salt pollution. The experiment involved an environmentally relevant 'pulse-exposure' design simulating three subsequent inflow events. Three sublethal endpoints were investigated, Filtration Activity, Transition Frequency (number of changes from opened to closed, or vice versa) and Avoidance Behavior. The mussels presented a high variation in filtration behavior, behaving asynchronously. At environmentally relevant de-icing salt exposure scenarios, A. anatina behavior patterns were significantly affected. Treated mussels' Filtration Activity decreased during periods of very high and long de-icing salt exposure (p<0.001), however, increased during short de-icing salt exposure. Treated mussels' Transition Frequency increased during periods of very high and long de-icing salt exposure (p<0.001), which mirrored the Avoidance Behavior endpoint observed only by mussels under chemical stress. Characteristics of Avoidance Behavior were tighter shell closures with repeated and irregular shell movements which was significantly different to their undisturbed resting behavior (p<0.001). Additionally, we found that mussels were sensitive to a chemical stressor even when the mussel's valves were closed. Due to the effects of de-icing salt pollution on freshwater mussel behavior, we suggest better management practices for de-icing salt use be implemented. Our experimental method demonstrated that, with the application of current technologies, mussel behavioral response to a chemical stressor can be measured. The tested sublethal endpoints are suitable for mussel ecotoxicology studies. Avoidance Behavior proved to be a potentially suitable endpoint for calculating mussel behavior effect concentration. Therefore we recommend adult mussel behavior as a suitable biomarker for future ecotoxicological research. This method could be applied to other bivalve species and for physical and environmental stressors, such as particulate matter and temperature.


Wheat bran fiber and development of adenomatous polyps: evidence from randomized, controlled clinical trials.
Mutations in oncogenes and tumor suppressor genes are thought to initiate and promote the pathway to colorectal cancer, leading to hyperproliferation, the development of adenomas, and progression to gross malignancy. Intervention at any of these steps can potentially prevent the development of cancer. Several randomized, controlled trials have investigated the effect of dietary interventions, including the addition of wheat bran fiber, on the development of adenomatous polyps. In a familial adenomatous polyposis trial, patients were treated with 4 g of ascorbic acid plus 400 mg of alpha-tocopherol per day alone or with a grain fiber supplement (22.5 g/day) over a 4-year period. On an actual-intake basis, the combined intervention inhibited the development of rectal polyps. However, the Toronto Polyp Prevention Trial found no significant differences in polyp recurrence rates between patients who were counseled to follow a low-fat, high-fiber diet and patients consuming a typical Western diet with placebo fiber. A 9-month study of patients with resected colon adenomas found that dietary wheat bran fiber significantly reduced total, primary, and secondary fecal bile acid concentrations and excretion rates. Such bile acid levels are thought to be related to the risk of developing cancer. The Australian Polyp Prevention Project reported that the combination of fat reduction and a supplement of wheat bran reduced the incidence of large colorectal adenomas. These latter results suggest that intervention with a low-fat wheat bran supplemented diet inhibits the transition from smaller to larger adenomas, which may be a critical step in determining which adenomas progress to malignancy.


The major cysteine proteinase (cruzipain) from Trypanosoma cruzi is antigenic in human infections.
Antibodies against the major cysteine proteinase (cruzipain) from Trypanosoma cruzi were detected in human sera obtained from patients with chronic Chagas' disease. Not only the intact 60-kDa enzyme but also its 25-kDa self-proteolysis fragment are antigenic in vivo. Although T. cruzi antigens 13 and 36 also reacted with the apparently monospecific antiproteinase serum, the antigenicity of cruzipain to human patients is genuine, since its reactivity was not modified by the adsorption of human sera with the recombinant proteins 13 and 36.


Impaired cardiac reserve and severely diminished skeletal muscle O₂ utilization mediate exercise intolerance in Barth syndrome.
Barth syndrome (BTHS) is a mitochondrial myopathy characterized by reports of exercise intolerance. We sought to determine if 1) BTHS leads to abnormalities of skeletal muscle O(2) extraction/utilization and 2) exercise intolerance in BTHS is related to impaired O(2) extraction/utilization, impaired cardiac function, or both. Participants with BTHS (age: 17 ± 5 yr, n = 15) and control participants (age: 13 ± 4 yr, n = 9) underwent graded exercise testing on a cycle ergometer with continuous ECG and metabolic measurements. Echocardiography was performed at rest and at peak exercise. Near-infrared spectroscopy of the vastus lateralis muscle was continuously recorded for measurements of skeletal muscle O(2) extraction. Adjusting for age, peak O(2) consumption (16.5 ± 4.0 vs. 39.5 ± 12.3 ml·kg(-1)·min(-1), P < 0.001) and peak work rate (58 ± 19 vs. 166 ± 60 W, P < 0.001) were significantly lower in BTHS than control participants. The percent increase from rest to peak exercise in ejection fraction (BTHS: 3 ± 10 vs. control: 19 ± 4%, P < 0.01) was blunted in BTHS compared with control participants. The muscle tissue O(2) saturation change from rest to peak exercise was paradoxically opposite (BTHS: 8 ± 16 vs. control: -5 ± 9, P < 0.01), and the deoxyhemoglobin change was blunted (BTHS: 0 ± 12 vs. control: 10 ± 8, P < 0.09) in BTHS compared with control participants, indicating impaired skeletal muscle extraction in BTHS. In conclusion, severe exercise intolerance in BTHS is due to both cardiac and skeletal muscle impairments that are consistent with cardiac and skeletal mitochondrial myopathy. These findings provide further insight to the pathophysiology of BTHS.


Catalytic Asymmetric Synthesis of Quaternary Barbituric Acids.
The catalytic asymmetric α-functionalization of prochiral barbituric acids, a subtype of pseudosymmetric 1,3-diamides, to yield the corresponding 5,5-disubstituted (quaternary) derivatives remains essentially unsolved. In this study 2-alkylthio-4,6-dioxopirimidines are designed as key 1,3-diamide surrogates that perform exceedingly in amine-squaramide catalyzed C-C bond forming reactions with vinyl ketones or Morita-Baylis-Hillmann-type allyl bromides as electrophiles. Mild acid hydrolysis of adducts affords barbituric acid derivatives with an in-ring quaternary carbon in unprecedented enantioselectivity, offering valuable materials for biological evaluations.


Risk preference shares the psychometric structure of major psychological traits.
To what extent is there a general factor of risk preference, R, akin to g, the general factor of intelligence? Can risk preference be regarded as a stable psychological trait? These conceptual issues persist because few attempts have been made to integrate multiple risk-taking measures, particularly measures from different and largely unrelated measurement traditions (self-reported propensity measures assessing stated preferences, incentivized behavioral measures eliciting revealed preferences, and frequency measures assessing actual risky activities). Adopting a comprehensive psychometric approach (1507 healthy adults completing 39 risk-taking measures, with a subsample of 109 participants completing a retest session after 6 months), we provide a substantive empirical foundation to address these issues, finding that correlations between propensity and behavioral measures were weak. Yet, a general factor of risk preference, R, emerged from stated preferences and generalized to specific and actual real-world risky activities (for example, smoking). Moreover, R proved to be highly reliable across time, indicative of a stable psychological trait. Our findings offer a first step toward a general mapping of the construct risk preference, which encompasses both general and domain-specific components, and have implications for the assessment of risk preference in the laboratory and in the wild.


[Erythrocytometric indicators of peripheral blood in hypothyroidism before and after treatment].
In studying the erythrocytometric peripheral blood indices in patients with hypothyroidism there was revealed an increase of the mean diameter, mean volume and thickness of the red blood cells. There was revealed that in the process of 4-week replacement therapy with lyothyronine-2-hydrochloride the patients with mild and moderately severe affection displayed an increase of the mean diameter of erythrocytes, a reduction of their thickness and volume and a fall of microcyte count. As to the patients with severe hypothyroidism--they show no significant dynamics of the erythrocytometric indices after one month of treatment.


A 3 year audit of fine needle aspirates from a symptomatic breast clinic.
A total of 2431 fine needle aspirates of symptomatic breast lumps was performed on 2096 patients over the last three years at the weekly head, neck and breast clinic at the Belfast City Hospital Trust. Diagnostic accuracy was achieved within the recommended standards although the "insufficient" rate was high at 31.8%. False negative and positive rates were low and the positive predictive value for malignancy was 99%. Excision biopsy for benign breast disease had decreased by almost a third during this period. Fine needle aspiration cytology is a highly accurate and cost-effective technique for the investigation of symptomatic breast lumps and results in significant savings.


Development of antibiotic resistance genes in microbial communities during long-term operation of anaerobic reactors in the treatment of pharmaceutical wastewater.
Biological treatment processes offer the ideal conditions in which a high diversity of microorganisms can grow and develop. The wastewater produced during these processes is contaminated with antibiotics and, as such, they provide the ideal setting for the acquisition and proliferation of antibiotic resistance genes (ARGs). This research investigated the occurrence and variation in the ARGs found during the one-year operation of the anaerobic sequencing batch reactors (SBRs) used to treat pharmaceutical wastewater that contained combinations of sulfamethoxazole-tetracycline-erythromycin (STE) and sulfamethoxazole-tetracycline (ST). The existence of eighteen ARGs encoding resistance to sulfamethoxazole (sul1, sul2, sul3), erythromycin (ermA, ermF, ermB, msrA, ereA), tetracycline (tetA, tetB, tetC, tetD, tetE, tetM, tetS, tetQ, tetW, tetX) and class Ι integron gene (intΙ 1) in the STE and ST reactors was investigated by quantitative real-time PCR. Due to the limited availability of primers to detect ARGs, Illumina sequencing was also performed on the sludge and effluent of the STE and ST reactors. Although there was good reactor performance in the SBRs, which corresponds to min 80% COD removal efficiency, tetA, tetB, sul1, sul2 and ermB genes were among those ARGs detected in the effluent from STE and ST reactors. A comparison of the ARGs acquired from the STE and ST reactors revealed that the effluent from the STE reactor had a higher number of ARGs than that from the ST reactor; this could be due to the synergistic effects of erythromycin. According to the expression of genes results, microorganisms achieve tetracycline and erythromycin resistance through a combination of three mechanisms: efflux pumping protein, modification of the antibiotic target and modifying enzymes. There was also a significant association between the presence of the class 1 integron and sulfamethoxazole resistance genes.


Effect of silica-based mesoporous nanomaterials on human blood cells.
Different mesoporous nanomaterials (MSNs) are constantly being developed for a range of therapeutic purposes, but they invariably interact with blood components and may cause hazardous side effects. Therefore, when designing and developing nanoparticles for biomedical applications, hemocompatibility should be one of the primary goals to assess their toxicity at the cellular level of all blood components. The aim of this study was to evaluate the compatibility of human blood cells (erythrocytes, platelets, and leukocytes) after exposure to silica-based mesoporous nanomaterials that had been manufactured using the sol-gel method, with Ca and Ce as doping elements. The viability of lymphocytes and monocytes was unaffected by the presence of MSNs at any concentration. However, it was found that all nanomaterials, at all concentrations, reduced the viability of granulocytes. P-selectin expression of all MSNs at all concentrations was statistically significantly higher in platelet incubation on the first day of storage (day 1) compared to the control. When incubated with MSNs, preserved platelets displayed higher levels of iROS at all MSNs types and concentrations examined. Ce-containing MSNs presented a slightly better hemocompatibility, although it was also dose dependent. Further research is required to determine how the unique characteristics of MSNs may affect various blood components in order to design safe and effective MSNs for various biomedical applications.


Human granulocyte colony-stimulating factor: biologic activities and receptor characterization on hematopoietic cells and small cell lung cancer cell lines.
Human granulocyte colony-stimulating factor (G-CSF) is a regulatory glycoprotein that stimulates the production of neutrophilic granulocytes from committed hematopoietic progenitor cells both in vitro and in vivo. In this report, we show that biosynthetic (recombinant) human G-CSF enhances colony formation by normal human bone marrow and the human myeloid leukemic cell lines, HL-60 and KG-1, as well as nonhematopoietic small cell lung cancer lines, H128 and H69. G-CSF also modulates multiple differentiated functions of human neutrophils, including enhanced oxidative metabolism in response to f-Met-Leu-Phe (f-MLP), increased antibody-dependent cell-mediated cytotoxicity (ADCC), and augmented arachidonic acid release in response to ionophore and chemotactic agents. These effects are all maximal at a concentration of 100 to 500 pmol/L. Using 125I-labeled recombinant human G-CSF, high affinity binding sites were identified on human neutrophils, the myeloid leukemia cell lines KG-1 and HL-60, and the small cell carcinoma cell lines, H128 and H69. G-CSF receptor numbers ranged between 138 and 285 sites per cell with a kd of 77 to 140 pmol/L, consistent with the concentrations of G-CSF that elicit biologic responses in vitro. Decreased specific binding of 125l-G-CSF by human neutrophils was consistently observed in the presence of excess unlabeled human granulocyte-macrophage colony-stimulating factor (GM-CSF), suggesting competition or down modulation by GM-CSF of the G-CSF receptor.


The role of p53-microRNA 200-Moesin axis in invasion and drug resistance of breast cancer cells.
This study aimed to analyze the expression of microRNAs in relation to p53 status in breast cancer cells and to delineate the role of Moesin in this axis. We used three isogenic breast carcinoma cell lines MCF7 (with wild-type p53), 1001 (MCF7 with mutated p53), and MCF7-E6 (MCF7 in which p53 function was disrupted). MicroRNA expression was analyzed using microarray analysis and confirmed by real-time polymerase chain reaction. The 1001 clone with mutant p53 showed 22 upregulated and 25 downregulated microRNAs. The predicted targets of these 47 microRNAs were >700 human genes belonging to interesting functional groups such as stem cell development and maintenance. The most significantly downregulated microRNAs in the p53-mutant cell line were from the miR-200 family. We focused on miR-200c which targets many transcripts involved in epithelial-to-mesenchymal transition including Moesin. We found that Moesin was expressed in 1001 but not in its p53 wild-type parental MCF7 consistent with the observed mesenchymal features in the 1001, such as vimentin positivity, E-cadherin negativity, and ZEB1 positivity in addition to the morphological changes. After Moesin silencing, the p53-mutant cells 1001 reverted from mesenchymal-to-epithelial phenotype and showed subtle reduction in migration and invasion and loss of ZEB1 and SNAIL expression. Interestingly, Moesin silencing restored the 1001 sensitivity to Doxorubicin. These results indicate that loss of miR-200c, as a consequence of p53 mutation, can upregulate Moesin oncogene and thus promote carcinogenesis. Moesin may play a role in metastasis and drug resistance of breast cancer.


Sensory neurotization of muscle: past, present and future considerations.
Research has shown that temporary innervation by a sensory neuron can provide trophic support to a denervated muscle and stave off muscular atrophy until motor neuron transfer is viable. This so called 'sensory protection' allows for improved outcomes when motor reinnervation able to occur. The theoretical benefit of sensory neurotization is hypothesized to maintain tissue architecture of the end organ due to tropic effects of stimulation. While the literature supports direct motor neurotization from 2 to 4 months post-injury, patient factors including the location of the injury and loss of nerve can preclude this therapeutic window. When direct neurotization is not possible, or there is a long distance to traverse for reinnervation, sensory neurotization may be beneficial. The theorized trophic stimulation enabling end organ architectural maintenance provided by sensory neurotization has been shown to allow for delayed direct motor neurotization without the irreversible sequelae of prolonged denervation. This is a review of the pathogenesis of nerve injury and a literature review of sensory neurotization. An analytical search of the literature in PubMed was performed in order to find articles pertinent to the topic of sensory neurotization, including experimental data from both animal models and case reports in humans.


TRAUMATIC LENS SUBLUXATION FROM PICKLEBALL INJURY: A CASE SERIES.
The purpose of this study was to describe two cases of traumatic lens subluxation resulting from pickleball injury. This is a case series. A 77-year-old man presented with worsening vision and was noted to have subluxation of his intraocular lens 10 days after being struck in the eye with a pickleball. The patient underwent a lens exchange with scleral fixation. A 76-year-old woman presented with blurry vision on the same day as her injury and was noted to have subluxation of her crystalline lens. She also underwent a lens insertion with scleral fixation. However, she experienced additional complications of postoperative cystoid macular edema and traumatic glaucoma. We recommend increased use of eye protection in pickleball.


Automated high-throughput siRNA transfection in raw 264.7 macrophages: a case study for optimization procedure.
RNAi using siRNA is a very powerful tool for functional genomics to identify new drug targets and biological pathways. Although their use in epithelial cells is relatively easy and straightforward, transfection in other cell types is still challenging. The authors report the optimization of transfection conditions for Raw 267.4 macrophage cells. The herein described procedure makes use of automated confocal microscopy, enhanced green fluorescent protein (EGFP)-expressing macrophages, and fluorescently labeled siRNAs to simultaneously quantify both siRNA uptake and silencing efficiency. A comparison of 10 commercial transfectants was performed, leading to the selection of the transfectant giving the highest reproducible knock-down effect without inducing cell toxicity or cell activation. Several buffers used for siRNA/lipid complex assembly were tested, and such a study revealed the crucial importance of this parameter. In addition, a kinetics study led to the determination of the optimal siRNA concentration and the best time window for the assay. In an original approach aimed at simultaneously optimizing both the high-throughput screening process and biological factors, optimal reagent volumes and a process flowchart were defined to ensure robust silencing efficiencies during screening. Such an account should pave the way for future genome-wide RNAi research in macrophages and present an optimization procedure for other "hard-totransfect" cell lines.


Health profile of highland Ethiopians in a small town in the south-western part of the country.
In conjunction with an investigation of nerve function tests of highland Ethiopians in an area of low endemicity of leprosy for 25-30 years, a comprehensive health survey was performed. We assessed 236 subjects, 118 females and 118 males, 177 students and 59 adults (Others) aged 10-75 years from Chencha woreda. We used a detailed medical, personal and social history, anthropomorphic measurements and complete physical examination. We identified six areas of medical concern: Intestinal parasite and diarrhoeal diseases affected 62%, despite treatment of all students and symptomatic adults the recurrence rate was high; skin diseases/conditions affected 88%; eye injections affected 26%; dental decay affected 33%; 20% had hypertension 14% requiring treatment; 11% gave a personal and/or family history of tuberculosis, 44% gave a history of BCG immunisation, while 34% had BCG scars, the lowest percentage (11%) being in students from Daramallo woreda. Supplies of clean water, effective disposal of human excreta and control of flies would greatly reduce intestinal, skin and eye infections. Regular tooth cleaning and possibly fluoridation of drinking water should improve dental health, with diet and exercise for young hypertensives. BCG immunisation in Chencha and Daramallo woredas (inaccessible areas) needs urgent attention.


Maternal preconceptional nutrition leads to variable fat deposition and gut dimensions of adult offspring mice (C57BL/6JBom).
Maternal nutrition during pregnancy or lactation may affect the chance of offspring becoming obese as adults, but little is known regarding the possible role of maternal nutrition before conception. In this study, we investigate how variable protein and carbohydrate content of the diet consumed before pregnancy affects fat deposition and gut dimensions of offspring mice. Eight-week-old female mice (C57BL/6JBom) were fed isocaloric low protein (8.4% protein; LP), standard protein (21.5% protein; ST) or high protein (44.2% protein; HP) diets. After 8 weeks of feeding, females were mated and fed a standard laboratory chow diet (22.5% protein) throughout periods of mating, gestation, lactation and weaning. Offspring mice were fed the same standard diet up to 46 days of age. Then offspring were killed and measures of dissected fat deposits and of the digestive system were taken. Fat deposition of the offspring was significantly affected by preconceptional maternal nutrition and the effects differed between sexes. Male offspring deposited most fat when mothers were fed the LP diet, whereas female offspring deposited most fat when mothers were fed the ST diet. The mass and length of the digestive organs were affected by preconceptional maternal nutrition. Total gut from pyloric sphincter to anus was significantly shorter and dry mass was heavier in mice whose mothers were fed LP diets compared with offspring of mothers fed ST diets or HP diets. There was no significant effect of maternal nutrition on dry mass of the stomach or ceca. Our study shows that preconceptional nutrition can have important influence on several body features of offspring in mice, including body composition and dimensions of the digestive system.


Structural basis of Ca2+-dependent activation and lipid transport by a TMEM16 scramblase.
The lipid distribution of plasma membranes of eukaryotic cells is asymmetric and phospholipid scramblases disrupt this asymmetry by mediating the rapid, nonselective transport of lipids down their concentration gradients. As a result, phosphatidylserine is exposed to the outer leaflet of membrane, an important step in extracellular signaling networks controlling processes such as apoptosis, blood coagulation, membrane fusion and repair. Several TMEM16 family members have been identified as Ca2+-activated scramblases, but the mechanisms underlying their Ca2+-dependent gating and their effects on the surrounding lipid bilayer remain poorly understood. Here, we describe three high-resolution cryo-electron microscopy structures of a fungal scramblase from Aspergillus fumigatus, afTMEM16, reconstituted in lipid nanodiscs. These structures reveal that Ca2+-dependent activation of the scramblase entails global rearrangement of the transmembrane and cytosolic domains. These structures, together with functional experiments, suggest that activation of the protein thins the membrane near the transport pathway to facilitate rapid transbilayer lipid movement.


Evaluating the Impact of Assessment Metrics for Simulated Central Venous Catheterization Training.
Performance assessment and feedback are critical factors in successful medical simulation-based training. The Dynamic Haptic Robotic Trainer (DHRT) allows residents to practice ultrasound-guided needle insertions during simulated central venous catheterization (CVC) procedures while providing detailed feedback and assessment. A study was performed to examine the effectiveness of the DHRT in training the important skills of needle tip tracking and aspiration and how these skills impact procedural complications in simulated CVC. The DHRT data were collected for 163 residents at 2 hospitals for 6 simulated needle insertions. Users were given automated feedback on 5 performance metrics, which measure aspiration rate, arterial punctures, punctures through and through the vein, loss of access to the vein, and successful access to the vein. Aspiration rates and tip tracking rates were analyzed to determine their significance in preventing CVC complications and improving performance. Tip tracking rates higher than 40% were 2.3 times more likely to result in successful venous access than rates less than 10%. Similarly, aspiration rates higher than 80% were 2.6 times more likely to result in successful venous access than rates less than 10%. Proper tip tracking and aspiration both reduced mechanical complications. Resident performance improved for all metrics except tip tracking. Proper tip tracking and aspiration both reduced complications and increased the likelihood of success. However, the skill of tip tracking was not effectively learned through practice without feedback. Therefore, ultrasound-guided needle-based procedures, including CVC, can be improved by providing specific feedback to users on their ultrasound usage to track needle insertions.


A new paraprobiotic-based treatment for control of Haemonchus contortus in sheep.
Haemonchus contortus is a critical parasite of goats and sheep. Infection by this blood-feeding gastrointestinal nematode (GIN) parasite has significant health consequences, especially in lambs and kids. The parasite has developed resistance to virtually all known classes of small molecule anthelmintics used to treat it, giving rise in some areas to multidrug resistant parasites that are very difficult to control. Thus, new anthelmintics are urgently needed. Bacillus thuringiensis (Bt) crystal protein 5B (Cry5B), a naturally occurring protein made by a bacterium widely and safely used around the world as a bioinsecticide, represents a new non-small molecule modality for treating GINs. Cry5B has demonstrated anthelmintic activities against parasites of monogastric animals, including some related to those that infect humans, but has not yet been studied in a ruminant. Here we show that H. contortus adults are susceptible to Cry5B protein in vitro. Cry5B produced in its natural form as a spore-crystal lysate against H. contortus infections in goats had no significant efficacy. However, a new Active Pharmaceutical Ingredient (API) paraprobiotic form of Cry5B called IBaCC (Inactivated Bacterium with Cytosolic Crystals), in which Cry5B crystals are encapsulated in dead Bt cell wall ghosts, showed excellent efficacy in vitro against larval stages of H. contortus and relative protein stability in bovine rumen fluid. When given to sheep experimentally infected with H. contortus as three 60 mg/kg doses, Cry5B IBaCC resulted in significant reductions in fecal egg counts (90%) and parasite burdens (72%), with a very high impact on female parasites (96% reduction). These data indicate that Cry5B IBaCC is a potent new treatment tool for small ruminants in the battle against H. contortus.


Developmental dysplasia of the hip: a history of innovation.
Developmental dysplasia of the hip (DDH) is a relatively common malady that has profound consequences in the infant if left untreated. Effective and early treatment of DDH has been praised as one of the most successful ventures of modern pediatric orthopedics. Yet, before the modern management of DDH came into existence, there were extensive technological developments in the field of harnesses, casts, and traction methods. This paper aims to identify the centuries-old history of advancement in DDH treatment and the many important people involved. Their devices, thoughts, and ideas continue to have a profound impact on the current practice of orthopedic surgery.


MicroRNA-135a Regulates Apoptosis Induced by Hydrogen Peroxide in Rat Cardiomyoblast Cells.
Oxidative stress and apoptosis are the most important pathologic features of ischemic heart disease. Recent research has indicated that microRNAs (miRs) play an essential role in apoptosis. However, whether miRs might regulate B cell lymphoma-2 (Bcl-2) protein in apoptosis during ischemic heart disease is still unclear. The aim of this study, therefore, was to confirm the regulation of microRNA-135a (miR-135a) in oxidative stress injuries induced by hydrogen peroxide (H2O2) in rat cardiomyoblast cells H9c2. To this end, we analyzed the effects of H2O2 treatment on miR-135a expression in rat cardiomyocytes. Furthermore, we upregulated and inhibited miR-135a using mimics and inhibitors, respectively, and examined the effects on cell viability and apoptosis-related proteins. We observed that miR-135a was markedly up-regulated under H2O2 treatment in rat cardiomyoblast cells. Overexpression of miR-135a blocked the Bcl-2 protein and enhanced the apoptosis induced by H2O2, and miR-135a inhibition restored Bcl-2 protein expression. Interestingly, miR-135a inhibition did not attenuate H2O2-induced apoptosis with Bcl-2 knockdown. The results of the present study indicate that miR-135a regulates H2O2-induced apoptosis in H9c2 cells via targeting Bcl-2, and that miR-135a may be a novel therapeutic target for ischemic heart disease.


Recent advances in neurosurgical techniques - historical considerations.
1. The basic principles of neurosurgery have changed but not as radically as we might believe. 2. The most radical changes include a full facility of power tools, the aid of magnification techniques with excellent illumination, and the great value of shrinking agents, with less damage to the assaulted brain. 3. The surgeon has been aided by a reclassification of tumors and thus can estimate his surgical attack and prognosis more accurately. History has not proven the malignant gliomas amenable to long-term surgical results, and out hopes must lie in chemotherapy. 4. The ancillary disciplines of neuroradiology and neuroanesthesia have aided the surgeon immeasurably in the planning of his operation, but the final results still depend basically on the surgeon's ability and judgment in that difficult decision "should I go for broke or stop?"


Rates of Missed Injuries in the Prehospital Setting Are Unrelated to the Gender of the Medical Provider: A Retrospective Study.
Medical organizations worldwide aim for equity and diversity in the medical profession to improve care quality. Data on whether the caregiver gender affects outcomes in the prehospital setting are essential but scarce compared to available in-hospital studies. To analyze the rates of missed injuries in the prehospital setting and determine whether these rates were associated with the gender of the on-field physician or paramedic. A retrospective record review was conducted, which included trauma records documented in two trauma registries, the prehospital Israel Defense Forces-Trauma Registry (IDF-TR), and the in-hospital Israeli National Trauma Registry (INTR). Missed injuries were defined as injuries documented in the INTR but not in the IDF-TR. A multivariable regression analysis was performed to assess the association between provider's gender and missed injuries. Of 490 casualties, 369 (75.3%) were treated by teams that included only male paramedics or physicians. In 386 (78.8%) cases, a physician was a part of the prehospital team. In all, 94 (19.2%) casualties sustained injuries that were missed by the prehospital medical team. Missed injuries were not associated with the gender of the paramedic or physician (odds ratio 1.242, 95% confidence interval 0.69-2.193). No association was found between the gender of the medical provider in the prehospital setting and the rate of missed injuries. These results should encourage prehospital emergency medical systems to aim for a balanced and diverse caregiver population.


Vitamin D Attenuates Kidney Fibrosis via Reducing Fibroblast Expansion, Inflammation, and Epithelial Cell Apoptosis.
Kidney fibrosis is the common final pathway of chronic kidney diseases (CKD). It is characterized by myofibroblast formation, inflammation, and epithelial architecture damage. Vitamin D is known as a renoprotective agent, although the precise mechanism is not well understood. This study aimed to elucidate the effect of vitamin D in fibroblast expansion, inflammation, and apoptosis in kidney fibrosis. We performed unilateral ureteral obstruction (UUO) in male Swiss-Webster background mice (3 months, 30-40 grams) to induce kidney fibrosis. The mice (n=25) were divided into five groups: UUO, 3 groups treated with different oral vitamin D doses (0.125 µg/kg (UUO+VD1), 0.25 µg/kg (UUO+VD2), and 0.5 µg/kg (UUO+VD3), and a Sham operation (SO) group with ethanol 0.2% supplementation. We sacrificed the mice on day14 after the operation and harvested the kidney. We made paraffin sections for histological analysis. Tubular injury and fibrosis were quantified based on periodic acid-Schiff (PAS) and Sirius Red (SR) staining. Immunostaining was done for examination of myofibroblasts (αSMA), fibroblasts (PDGFRβ), TLR4, and apoptosis (TUNEL). We did RNA extraction and cDNA for Reverse transcriptase PCR (RT-PCR) experiment for measuring MCP-1, ICAM-1, TLR4, and collagen 1 expression. TGFβ1 level was quantified using ELISA. We observed a significantly lower levels of fibrosis (p<0.001), tubular injury scores (p<0.001), and myofibroblast areas (p<0.001) in the groups treated with vitamin D compared with the UUO group. The TGFβ1 levels and the fibroblast quantifications were also significantly lower in the former group. However, we did not find any significant difference among the various vitamin D-treated groups. Concerning the dose-independent effect, we only compared the UUO+VD-1 group with SO group and found by TUNEL assay that UUO+VD-1 had a significantly lower epithelial cell apoptosis. RT-PCR analysis showed lower expression of collagen1, as well as inflammation-mediator expression (MCP-1, ICAM-1, TLR4) in the UUO+VD-1 group compared with the SO group. Vitamin D reduces kidney fibrosis through inhibition of fibroblast activation, and ameliorates epithelial cell architecture.


X-ray phase vortices: theory and experiment.
We review the current work on x-ray phase vortices. We explain the role of an x-ray vortex in phase recovery and speculate on its possible applications in other fields of x-ray optical research. We present our theoretical understanding of the structure of phase vortices and test these predictions against experiment. We present experimental observations of phase vortices with charge greater than 3 and observe that their propagation appears to be consistent with our theoretical models.


Selective CXCR4 antagonism by Tat: implications for in vivo expansion of coreceptor use by HIV-1.
Chemokines and chemokine receptors play important roles in HIV-1 infection and tropism. CCR5 is the major macrophage-tropic coreceptor for HIV-1 whereas CXC chemokine receptor 4 (CXCR4) serves the counterpart function for T cell-tropic viruses. An outstanding biological mystery is why only R5-HIV-1 is initially detected in new seroconvertors who are exposed to R5 and X4 viruses. Indeed, X4 virus emerges in a minority of patients and only in the late stage of disease, suggesting that early negative selection against HIV-1-CXCR4 interaction may exist. Here, we report that the HIV-1 Tat protein, which is secreted from virus-infected cells, is a CXCR4-specific antagonist. Soluble Tat selectively inhibited the entry and replication of X4, but not R5, virus in peripheral blood mononuclear cells (PBMCs). We propose that one functional consequence of secreted Tat is to select against X4 viruses, thereby influencing the early in vivo course of HIV-1 disease.


RESPITE--a computer-aided guide to the prevalence of pneumonia in pig herds.
An interactive computer-based guide (termed RESPITE) was developed to demonstrate to pig producers the expected level of pneumonia in pig herds which follow specified management practices known to influence the severity of pneumonia problems. A program was used to evaluate the combined effect of known risk factors present in the particular herd on the prevalence of lung lesions in slaughter pigs. The expected prevalence was estimated using formulae that were derived from observations and data in the published literature. Eleven risk factors considered are the number of pigs in the same room, all-in/all-out versus continuous flow of pigs, closed versus open herd, temperature fluctuation ratio, width of the buildings, space allotted per pig, the type of partitions separating adjacent pens, the presence or absence of diarrhoea as a clinical problem, liquid versus solid manure disposal, ascarid control efficiency, and the presence or absence of active Aujeszky's disease in the herd. Each of the factors can be assessed in the farrowing, nursery and grow-finish stages of production and the appropriate observations are entered. The computer uses the data to calculate the expected prevalence of pneumonia in animals leaving that stage of production. Of the pneumonia developing in the farrowing, nursery and grow-finish stages, 90 per cent, 75 per cent and 25 per cent respectively is considered to resolve before slaughter inspection at 100 kg. Adjusting for this degree of resolution, the program then estimates the expected final prevalence of pneumonic lesions in slaughter pigs. Comparison of predictions with slaughterhouse data from four herds indicated that the guide was realistic in its estimates.


Autistic-like social deficits in hippocampal MeCP2 knockdown rat models are rescued by ketamine.
Autism or autism spectrum disorder (ASD) is a behavioral syndrome characterized by persistent deficits in social interaction, and repetitive patterns of behavior, interests, or activities. The gene encoding Methyl-CpG binding protein 2 (MeCP2) is one of a few exceptional genes of established causal effect in ASD. Although genetically engineered mice studies may shed light on how MeCP2 loss affects synaptic activity patterns across the whole brain, such studies are not considered practical in ASD patients due to the overall level of impairment, and are technically challenging in mice. For the first time, we show that hippocampal MeCP2 knockdown produces behavioral abnormalities associated with autism-like traits in rats, providing a new strategy to investigate the efficacy of therapeutics in ASD. Ketamine, an N-Methyl-D-aspartate (NMDA) blocker, has been proposed as a possible treatment for autism. Using the MeCP2 knockdown rats in conjunction with a rat model of valproic acid (VPA)-induced ASD, we examined gene expression and ASD behaviors upon ketamine treatment. We report that the core symptoms of autism in MeCP2 knockdown rats with social impairment recovered dramatically following a single treatment with ketamine. [BMB Reports 2022; 55(5): 238-243].


FDG positron emission tomography in the diagnosis of peripheral pulmonary focal lesions.
Positron emission tomography (PET) using fluoride-18-marked fluoride deoxyglucose (FDG) represents a metabolically based imaging technique capable of providing information on the potential malignancy of peripheral pulmonary focal lesions. In the present prospective study, we investigated the effectiveness of FDG-PET in determining the dignities of 67 such lesions in 35 patients. Findings of FDG-PET were compared with those of computed tomography (CT), as well as with surgical and histological reports, and the value of FDG-PET as a diagnostic method evaluated. FDG-PET correctly identified 38 lesions as positive for malignancy, 18 correctly as negative, 7 incorrectly as negative, and 4 incorrectly as positive. Based on lesions, this yields a sensitivity of 84.4% and a specificity of 81.8%. All malignant focal lesions with a diameter of over 1.2 cm were correctly identified (sensitivity: 100%). In cases of intense FDG uptake, differentiation between a primary lesion, a metastasis, and an acute inflammation is often not possible.


A Novel Passive Method for the Assessment of Skin-Electrode Contact Impedance in Intraoperative Neurophysiological Monitoring Systems.
Intraoperative Neurophysiological Monitoring is a set of monitoring techniques consisting of reading electrical activity generated by the nervous system structures during surgeries. In order to guarantee signal quality, contact impedance between the sensing electrodes and the patient's skin needs to be as low as possible. Hence, monitoring this impedance while signals are measured is an important feature of current medical devices. The most commonly used technique involves injection of a known current and measurement of the voltage drop in the contact interface. This method poses several problems, such as power consumption (critical in battery-powered systems), frequency dependency and regulation issues, which are overcome by using a passive method. The fundamentals of the method proposed in this paper are based on the utilization of the variation suffered by the input random signal when a known resistance is connected in parallel to the input terminals of the low-noise amplifier (LNA) of the analog front-end of the acquisition system. Controlling the connection of the resistors and computing the root mean square of the LNA output voltage has been proved to be a useful tool to assess that the contact impedance is suitably low, allowing the user to know if the neural measurements obtained are valid.


A framework for exploring adolescent wellness.
This article presents and explains a "Framework for Exploring Adolescent Wellness" and outlines a research approach used to explore adolescent wellness specific to the discipline of nursing. The "Framework for Exploring Adolescent Wellness" assessed the concept of wellness through the perceptions of youth and sought to explain the relationship between adolescent well-being and development. A wellness survey was used to collect data from 280 youth, 16 to 20 years old, in two Western Canadian high schools. Their perceptions of wellness meant more to them than regular physical activity and healthy eating. The majority of youth suggested that psychological (89%), social (85%), and physical (80%) development made the most significant contribution to adolescent wellness. Slightly more than half the youth felt that spirituality (53%) contributed to their sense of wellness. These research findings indicate the need for an approach to adolescent nursing care that includes a high priority and greater visibility to the practice and philosophy of wellness.


[Comparison of two hemagglutination tests for hepatitis B surface antigen (author's transl)].
Two commercial reverse passive hemagglutination tests of HBsAg (Organon and Wellcome) were compared and our results showed that both of them had excellent sensitivities. However, Wellcome excelled in specificities. The false positive test should be prevented by pretreatment of the serum. The hemagglutination may be comparable to the radioimmunoassay, if the specimens are adequately pretreated.


[Allergies to dental metals. Titanium: a new allergen].
Oral allergies are underdiagnosed by dental health professionals. Patients with an oral allergy complain of various symptoms such as burning or tingling sensations, with or without oral dryness or loss of taste, or of more general symptoms such as headache, dyspepsia, asthenia, arthralgia, myalgia. The signs of oral allergy include erythema, labial oedema or purpuric patches on the palate, oral ulcers, gingivitis, geographical tongue, angular cheilitis, perioral eczematous eruption, or lichenoid reactions localized on the oral mucosa. There is an increase in the prevalence of oral allergies to metals used in dental materials. Allergy to gold included in dental prosthesis has been well documented since the years eighties. Recently, titanium, used in orthopedic devices and oral implants, considered as an inert material, can induce toxicity or allergic type I or IV reactions. These reactions to titanium could be responsible for unexplained successive failure cases of dental implants in some patients (named "cluster patients"). The risk of an allergy to titanium is increased in patients who are allergic to other metals. In these patients, an evaluation of allergy is recommended, in order to exclude any problem with titanium medical devices. We stress the importance of a multidisciplinary approach to take into account patients with an oral allergy, with participation of specialists from dental and dermatologic fields.


Apparent Diffusion Coefficient Value Changes and Clinical Correlation in 90 Cases of Cytomegalovirus-Infected Fetuses with Unremarkable Fetal MRI Results.
Cytomegalovirus is the leading intrauterine infection. Fetal MR imaging is an accepted tool for fetal brain evaluation, yet it still lacks the ability to accurately predict the extent of the neurodevelopmental impairment, especially in fetal MR imaging scans with unremarkable findings. Our hypothesis was that intrauterine cytomegalovirus infection causes diffusional changes in fetal brains and that those changes may correlate with the severity of neurodevelopmental deficiencies. A retrospective analysis was performed on 90 fetal MR imaging scans of cytomegalovirus-infected fetuses with unremarkable results and compared with a matched gestational age control group of 68 fetal head MR imaging scans. ADC values were measured and averaged in the frontal, parietal, occipital, and temporal lobes; basal ganglia; thalamus; and pons. For neurocognitive assessment, the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) was used on 58 children in the cytomegalovirus-infected group. ADC values were reduced for the cytomegalovirus-infected fetuses in most brain areas studied. The VABS-II showed no trend for the major domains or the composite score of the VABS-II for the cytomegalovirus-infected children compared with the healthy population distribution. Some subdomains showed an association between ADC values and VABS-II scores. Cytomegalovirus infection causes diffuse reduction in ADC values in the fetal brain even in unremarkable fetal MR imaging scans. Cytomegalovirus-infected children with unremarkable fetal MR imaging scans do not deviate from the healthy population in the VABS-II neurocognitive assessment. ADC values were not correlated with VABS-II scores. However, the lack of clinical findings, as seen in most cytomegalovirus-infected fetuses, does not eliminate the possibility of future neurodevelopmental pathology.


Molecular Mechanisms of Psilocybin and Implications for the Treatment of Depression.
Therapeutic deficiencies with monoaminergic antidepressants invites the need to identify and develop novel rapid-acting antidepressants. Hitherto, ketamine and esketamine are identified as safe, well-tolerated rapid-acting antidepressants in adults with treatment-resistant depression, and also mitigate measures of suicidality. Psilocybin is a naturally occurring psychoactive alkaloid and non-selective agonist at many serotonin receptors, especially at serotonin 5-HT2A receptors, and is found in the Psilocybe genus of mushrooms. Preliminary studies with psilocybin have shown therapeutic promise across diverse populations including major depressive disorder. The pharmacodynamic mechanisms mediating the antidepressant and psychedelic effects of psilocybin are currently unknown but are thought to involve the modulation of the serotonergic system, primarily through agonism at the 5-HT2A receptors and downstream changes in gene expression. It is also established that indirect effects on dopaminergic and glutamatergic systems are contributory, as well as effects at other lower affinity targets. Along with the direct effects on neurochemical systems, psilocybin alters neural circuitry and key brain regions previously implicated in depression, including the default mode network and amygdala. The aim of this review is to synthesize the current understanding of the receptor pharmacology and neuronal mechanisms underlying the psychedelic and putative antidepressant properties of psilocybin.


Near-channel classifier: symbiotic communication and classification in high-dimensional space.
Brain-inspired high-dimensional (HD) computing represents and manipulates data using very long, random vectors with dimensionality in the thousands. This representation provides great robustness for various classification tasks where classifiers operate at low signal-to-noise ratio (SNR) conditions. Similarly, hyperdimensional modulation (HDM) leverages the robustness of complex-valued HD representations to reliably transmit information over a wireless channel, achieving a similar SNR gain compared to state-of-the-art codes. Here, we first propose methods to improve HDM in two ways: (1) reducing the complexity of encoding and decoding operations by generating, manipulating, and transmitting bipolar or integer vectors instead of complex vectors; (2) increasing the SNR gain by 0.2 dB using a new soft-feedback decoder; it can also increase the additive superposition capacity of HD vectors up to 1.7[Formula: see text] in noise-free cases. Secondly, we propose to combine encoding/decoding aspects of communication with classification into a single framework by relying on multifaceted HD representations. This leads to a near-channel classification (NCC) approach that avoids transformations between different representations and the overhead of multiple layers of encoding/decoding, hence reducing latency and complexity of a wireless smart distributed system while providing robustness against noise and interference from other nodes. We provide a use-case for wearable hand gesture recognition with 5 classes from 64 EMG sensors, where the encoded vectors are transmitted to a remote node for either performing NCC, or reconstruction of the encoded data. In NCC mode, the original classification accuracy of 94% is maintained, even in the channel at SNR of 0 dB, by transmitting 10,000-bit vectors. We remove the redundancy by reducing the vector dimensionality to 2048-bit that still exhibits a graceful degradation: less than 6% accuracy loss is occurred in the channel at - 5 dB, and with the interference from 6 nodes that simultaneously transmit their encoded vectors. In the reconstruction mode, it improves the mean-squared error by up to 20 dB, compared to standard decoding, when transmitting 2048-dimensional vectors.


Addressing maternal depression in home visiting: Findings from the home visiting collaborative improvement and innovation network.
Maternal depression is common among low-income women enrolled in home visiting programs, yet there is considerable variability in the extent to which it is identified and addressed. This study examines outcomes related to postpartum depression screening, receipt of evidence-based services, and reductions in depressive symptoms among clients of home visiting programs in the Health Resources and Services Administration's Maternal, Infant, and Early Childhood Home Visiting Program Home Visiting Collaborative Improvement and Innovation Network (HV CoIIN), the first U.S. national application of the Institute for Healthcare Improvement's Breakthrough Series (BTS) Model in home visiting programs. Fourteen home visiting programs in eight states, serving a geographically and racially diverse caseload of pregnant women and new mothers, took part in the HV CoIIN. Women in participating home visiting programs received the intervention strategies implemented by their program during participation in the collaborative. HV CoIIN strategies included specific policies and protocols for depression screening and home visitor response to screening results; home visitor training and supervision; delivery of prevention and treatment interventions; and tracking systems for screening, referral, and follow-up. HV CoIIN's proposed primary outcome was that 85% of women who accessed evidence-based services would experience a 25% reduction in depressive symptoms three months after accessing services. Secondary outcomes included an increased percentage of women who were screened for depression within three months of enrollment or birth, who verbally accepted a referral to evidence-based services, and who received one or more evidence-based service contacts. HV CoIIN resulted in improved symptoms among women who accessed services, from 51.1% to 59.9%. HV CoIIN also improved the percent of women screened for depression, from 83.6% to 96.3%, and those with positive depression screens who accessed evidence-based services, from 41.6% to 65.5%. Home visiting programs in this study were early adopters of quality improvement activities, which may limit the generalizability of these results to other home visiting programs. Home visiting programs can play an important role in closing gaps in maternal depression identification, referrals, service access, and symptom alleviation. Continuous quality improvement and BTS collaborative methods can be used to improve home visiting services in ways that advance national public health priorities and improve population health outcomes.


Malignant collision tumors in two dogs.
CASE DESCRIPTION A 13-year-old Labrador Retriever with a 4-cm-diameter ulcerated perianal mass and a 12-year-old Golden Retriever with a 5-cm-diameter ulcerated caudolateral abdominal mass were brought to a referral oncology practice for evaluation of the dermal masses. Both masses were resected with wide margins without reported postoperative complications. For both dogs, a diagnosis of collision tumor was made. The database of the Veterinary Diagnostic Laboratories at Colorado State University was searched for other examples of collision tumors in dogs. CLINICAL FINDINGS Histologic assessment of the masses revealed collision tumors in both patients. The perianal mass was diagnosed as a perianal gland carcinoma with adjacent hemangiosarcoma. The flank mass was diagnosed as a fibrosarcoma with an adjacent mast cell tumor. The university database search of sample submissions in 2008 through 2014 for the keywords collision, admixed, or adjacent yielded 37 additional cases of dogs with malignant nontesticular collision tumors. TREATMENT AND OUTCOME Both dogs were treated with surgery alone and received no adjunctive treatments. Both tumors were completely excised. There was no evidence of either local tumor recurrence or metastasis in the Labrador Retriever and the Golden Retriever at 1,009 and 433 days after surgery, respectively. CLINICAL RELEVANCE Collision tumors are rare, and there is minimal information regarding treatment recommendations and outcome for animals with collision tumors. On the basis of the 2 cases described in this report, the outcome associated with treatment of collision tumors may be similar to the expected outcome for treatment of any of the individual tumor types in dogs.