The metabolic chiral inversion and dispositional enantioselectivity of the 2-arylpropionic acids and their biological consequences.
The 2-arylpropionic acids are currently an important group of non-steroidal anti-inflammatory agents. They contain a chiral centre, and in vitro studies on inhibition of prostaglandin synthesis show that their activity resides almost exclusively in the S(+)-isomers. However, this stereoselectivity of action is not manifest in vivo, due to the thus-far-unique unidirectional metabolic inversion of the chiral centre from the inactive R(-)-isomers to the S(+)-antipodes. Available evidence strongly suggests that this reaction proceeds via the formation of the acyl CoA thioesters of the 2-arylpropionates, but the participation of enzyme(s) in the inversion process remains uncertain. Although the chiral inversion is seemingly a general feature of the fate of 2-arylpropionates, there do occur important combinations of acid and species where the reaction is not extant. The stereochemistry of the chiral centre of these acids also influences other aspects of their disposition, including the oxidative metabolism of the aryl/arylakyl moiety, glucuronidation of the -COOH group and plasma protein binding, and the importance of certain of these becomes more evident when renal function is impaired. The biological consequences of the metabolic chiral inversion and enantioselective disposition of the 2-arylpropionates have been summarized in terms of their implications for the development and use of safer and more effective drugs of this class.


Danger is only skin deep: aggressive epidermal carcinomas. An overview of the diagnosis, demographics, molecular-genetics, staging, prognostic biomarkers, and therapeutic advances in Merkel cell carcinoma.
Merkel cell carcinoma (MCC) is a high grade primary cutaneous neuroendocrine carcinoma and is among the most aggressive cutaneous malignancies. The rising incidence of MCC, together with its often rapidly aggressive course, underscore a critical need to recognize the histopathologic and the immunohistochemical features that inform its accurate diagnosis. In the current review, we summarize the current state of knowledge regarding the accurate diagnosis of MCC and the exclusion of other entities in the differential diagnosis. We provide a comprehensive review of genomic studies that identified the molecular-genetic drivers of MCC as well as a summary of studies identifying prognostic biomarkers that can facilitate risk stratification. Importantly, Merkel cell polyomavirus (MCPyV) appears to be causative in most cases of MCC and represents both a diagnostic and prognostic marker. Finally, as staging of MCC has undergone critical refinements with the introduction of the 8th Edition of the American Joint Committee on Cancer staging system, we provide an update on MCC staging. In particular, the prognostic significance of the sentinel lymph node (SLN) in MCC necessitates a systematic approach to its evaluation and diagnosis to ensure accurate and consistent risk stratification for patients, and we therefore provide a comprehensive overview of SLN evaluation in MCC. Finally, the intimate relationship between MCC and the integrity of the host immune system has led to paradigm-shifting therapeutic advances with the successful application of immune checkpoint blockade to treat patients with advanced disease, and we therefore summarize those studies and the correlative studies in which predictive biomarkers have been identified.


Effect of Lactobacillus delbrueckii subsp. lactis on vaginal radiotherapy for gynecological cancer.
The aim of this study was to evaluate the effect of Lactobacillus delbrueckii subsp. lactis (L.del) on vaginal microbiota (VM) dysbiosis and vaginal radiation injury in gynecologic cancer patients. The inhibitory effects of L.del on cervical cancer cells were also studied in vitro. Gynecologic cancer patients receiving radiotherapy were randomized into control and L.del intervention groups. The control group received radiotherapy, while the intervention group received radiotherapy and L.del intervention (1 capsule/day placed into the deep vagina from the first day of radiotherapy until the end of treatment). Vaginal swab samples were collected on the first day pre-treatment and the last day post-treatment. DNA from 54 patients was extracted and assessed by the 16S rRNA sequencing method. Radiotherapy resulted in vaginal microbiome dysbiosis characterized by increased phylogenetic diversity and increased abundance of Brevundimonas, Streptococcus and Prevotella, but a decreased abundance of Lactobacillus. Level 2 vaginal radiation injury was positively associated with the abundance of Brevundimonas and gram-negative non-fermenting bacteria. Administration of L.del attenuated the reduction of Lactobacillus while also inhibiting the abundance of Streptococcus and Prevotella, thereby ameliorating radiotherapy-related vaginal microbiota dysbiosis. CLD inhibited the in vitro proliferation of SiHa cells by altering the expression of BCL2, HPV16-E6, HPV16-E7, IL6, MAP7, BAX, Caspase-3, Caspase-9 and LTF. In conclusion, L. del application can alleviate radiation-induced vaginal dysbiosis and restore Lactobacillus dominance of the vaginal microbiome. Moreover, CLD was found to inhibit cell growth and promote the apoptosis of SiHa cells in vitro. The registration number for this clinical trial is ChiCTR1900021784.


Skin characteristics of Chinese men and their beard removal habits.
Grooming habits of men in China have some marked differences from those in other areas in the world, with a high percentage of men resorting to shaving with an electric razor. This is influenced by multiple factors, such as a lower facial hair growth density concentrated in a small area around the mouth. Further, there is limited knowledge and misconceptions around the alleged negative skin effects of blade shaving. To compare skin in the shaved area with that of the rest of the face, and to compare the impact of shaving with a modern three-blade razor vs. electric shaving. Pilot clinical studies including 50 and 40 healthy Chinese men, respectively. Skin in the shaved area is different from the rest of the face, with a higher temperature, lower hydration and diminished skin barrier function. Regular shaving with a modern multiblade razor was not statistically different from dry shaving in terms of impact on barrier function. Shaving with a modern multiblade razor could even deliver certain skin benefits in the area of facial oil control and reducing skin flakes.


Preformulation studies of dovitinib free base: Solubility, lipophilicity and stability.
Dovitinib has been investigated as an anti-tumor drug due to its ability to inhibit multiple receptor tyrosine kinases. Dovitinib free base has a poor water solubility leading to poor absorption. Salts and lipid-based formulations have been used to improve drug availability. Here, we investigated the physiochemical properties of the dovitinib free base in the presence of some pharmaceutical excipients. We sought to study the effect of acidic counterions on the aqueous solubility and lipophilicity of dovitinib and how pH, buffer species, and cyclodextrin (CD) influenced dovitinib stability. pH-solubility studies were performed by titration against five different acids. Aqueous solubility of dovitinib salt depended on the counterion. Lactic acid greatly increased the aqueous solubility of dovitinib. The counterion effect on the solubility was also investigated in the aqueous complexing media. Unexpected synergistic solubilization was found with γ-CD/phosphoric acid and γ-CD/maleic acid. The counterion did not affect the lipophilicity of dovitinib at physiological pH. Accelerated degradation of dovitinib was carried out at high temperature. Stability was studied across a range of pH values, buffer species and in the presence of two CDs. Dovitinib was most stable at pH 4 in the phosphate buffer species. γ-CD stabilized the drug at relatively low pH.


Tissue oxygenation of the skeletal muscle and of the heart during hemodynamic alterations in rats.
In the anaesthetized, open-chest rat, electrical stimulation of the sympathetic or parasympathetic nerves in the cervical area produced significant changes in the heart rate. The subsequent alterations in cardiac output and in total peripheral resistance did not alter the oxygenation of resting skeletal muscle. This means that the skeletal muscle of intact rats provided sufficient O2 to withstand shortlasting changes in hemodynamics. The increase in mean tissue PO2 on the heart after the bilateral vagotomy was the consequence of an increased perfusion due to the increased heart rate. The absence of vasoconstrictor nerve impulses after the bilateral dissection of the sympathetic cord induced a dilation of the vascular bed and therefore an increase in the tissue PO2 of the heart.


Soluble factor(s) released by the PF-382 T-cell line enhances the stimulatory effect of monocytes on the BFU-E growth.
PF-382 is a human T-cell line that has been shown to elaborate factors that modulate normal hemopoiesis in vitro. In the present study we report that this cell line constitutively releases in both serum-containing and serum-free supernatants a potent enhancer of BFU-E growth. The factor(s), partially purified by gel filtration, is a heat-stable molecule(s) degradable by trypsin and 2-mercaptoethanol treatments, equally active on bone marrow and peripheral blood erythroid progenitor cells, but not on CFU-GM. Unlike other sources of BPA, this stimulatory factor(s) exerts its effect in the presence of mononuclear adherent cells. In fact, the addition of conditioned medium obtained by 48 hr preincubation of isolated monocytes with 10% PF-382 supernatant (M-CM2) or the concomitant addition of supernatant from PF-382 cells (PF-382-CM) and from unstimulated monocytes (M-CM1) are capable of fully replacing the presence of monocytes in the BFU-E assay. Since the independent addition of PF-382-CM or of M-CM1 is devoid of stimulatory function, we suggest that the PF-382 derived BFU-E growth inducer, which differs from IL-1, IL-3, IL-4, GM and G-CSF, exerts its activity "via" a synergistic mechanism with a monokine.


Thy-1 predicts poor prognosis and is associated with self-renewal in ovarian cancer.
Ovarian cancer is the leading cause of gynecologic cancer death in the United States despite effective first-line systemic chemotherapy. Cancer stem cells (CSCs) retain the ability to self-renew and proliferate and may be a means of harboring disease that evades standard treatment strategies. We previously performed a high-throughput screen to assess differential protein expression in ovarian CSCs compared to non-CSCs and observed that Thy-1 was more highly expressed in CSCs. Our primary aim was to validate Thy-1 (CD90) as a cancer stem cell (CSC) marker in epithelial ovarian cancer (EOC), correlate with clinical outcomes, and assess as a potential therapeutic target. Kaplan Meier (KM) Plotter data were correlated with survival outcomes. Quantitative real-time PCR, flow cytometry, and immunoblots assessed RNA and protein expression. Limiting dilution assays assessed self-renewal capacity and proliferation assays assessed proliferative capacity. RNA in-situ hybridization was performed on patient specimens to assess feasibility. Thy-1 (CD90) is more highly expressed in ovarian CSCs than non-CSCs, in EOC compared to benign ovarian epithelium (P < 0.001), and is highest in serous EOC (P < 0.05). Serous ovarian cancers with high Thy-1 expression have poorer outcomes (median PFS 15.8 vs. 18.3 months, P = 0 < 0.001; median OS 40.1 v. 45.8 months, P = 0.036). Endometrioid ovarian cancers with high Thy-1 have poorer PFS, but no difference in OS (upper quartile PFS 34 v. 11 months, P = 0.013; quartile OS not reached, P = 0.69). In vitro, Thy-1 expression is higher in CSCs versus non-CSCs. EOC cells with high Thy-1 expression demonstrate increased proliferation and self-renewal. Thy-1 knockdown in EOC cells decreases proliferative capacity and self-renewal capacity, and knockdown is associated with decreased expression of stem cell transcription factors NANOG and SOX2. RNA in situ hybridization is feasible in ovarian cancer tissue specimens. Thy-1 is a marker of ovarian CSCs. Increased expression of Thy-1 in EOC predicts poor prognosis and is associated with increased proliferative and self-renewal capacity. Thy-1 knockdown decreases proliferative and self-renewal capacity, and represents a potential therapeutic target.


Production of CaCO3/hyperbranched polyglycidol hybrid films using spray-coating technique.
Biomineralizing organisms employ macromolecules and cellular processing strategies in order to produce highly complex composite materials such as nacre. Bionic approaches translating this knowledge into viable technical production schemes for a large-scale production of biomimetic hybrid materials have met with limited success so far. Investigations presented here thus focus on the production of CaCO(3)/polymer hybrid coatings that can be applied to huge surface areas via reactive spray-coating. Technical requirements for simplicity and cost efficiency include a straightforward one-pot synthesis of low molecular weight hyperbranched polyglycidols (polyethers of 2,3-epoxy-1-propanol) as a simple mimic of biological macromolecules. Polymers functionalized with phosphate monoester, sulfate or carboxylate groups provide a means of controlling CaCO(3) particle density and morphology in the final coatings. We employ reactive spray-coating techniques to generate CaCO(3)/hybrid coatings among which vaterite composites can be prepared in the presence of sulfate-containing hyperbranched polyglycidol. These coatings show high stability and remained unchanged for periods longer than 9 months. By employing carboxylate-based hyperbranched polyglycidol, it is possible to deposit vaterite-calcite composites, whereas phosphate-ester-based hyperbranched polyglycidol leads to calcite composites. Nanoindentation was used to study mechanical properties, showing that coatings thus obtained are slightly harder than pure calcite.


Etiologic diagnosis of corneal ulceration at a tertiary eye center in Kathmandu, Nepal.
To determine the etiologic diagnosis of infectious corneal ulcers at Tilganga Institute of Ophthalmology, a tertiary teaching hospital in Kathmandu Nepal, from 2006-2009. This study involved a review of all microbiology records at Tilganga Institute of Ophthalmology from August 2006 through July 2009. Microbiologic records from the corneal scrapings of all patients suspected of having infectious corneal ulcers were included. Corneal scrapings were obtained from 468 patients. The average patient age was 52 years, and 55% of the affected cases were males. Microorganisms were grown from 185 of the corneal scrapings (40%). Pure bacterial cultures were obtained from 72 patients (39%), and pure fungal cultures were obtained from 113 patients (61%). Gram stain was 75% sensitive (95% confidence interval, 0.632-0.841) in identifying bacterial infection, whereas KOH prep was 80.5% sensitive (95% confidence interval, 0.718-0.871) in identifying fungal organisms. Of 72 bacterial isolates, 50 isolates (69%) were Streptococcus pneumoniae, the most common organism isolated in this study. Of 113 fungal isolates, 40 of isolates (35%) were identified as Aspergillus sp. Fungal organisms (61%) are the most common cause of infectious keratitis in this patient population. Of all organisms, S. pneumoniae was the most common organism identified. Smear microscopy is reliable in rapidly determining the etiology of the corneal infection and can be used to help guide initial therapy in this setting.


Malaria parasite and vector genomes: partners in crime.
The publication of the genome sequences of the malaria parasite Plasmodium falciparum and the insect vector Anopheles gambiae paves the way for scientists to study these organisms by using technologies developed to observe global changes in transcription and translation, as well as computational tools. Researchers are now able to investigate complex changes involved in development, growth and reaction to external factors. Given the medical importance of these organisms, much of this work is targeted on drug or insecticide discovery (including mechanisms of resistance to existing treatments), but the genome information also provides the opportunity to develop novel therapies.


A longitudinal analysis of artificial insemination with donor semen.
A longitudinal analysis of artificial insemination with donor semen (AID) in 114 consecutive couples revealed a 37% over-all pregnancy rate. The 45 pregnancies occurred in 39 patients, and approximately 90% of these pregnancies occurred within six cycles of AID. Pregnancy rates were higher in the age group 25 to 30, in those who received only fresh semen, and in those with a history of a previous pregnancy. Lower pregnancy rates were observed in patients age 31 or older, in those with pelvic disease, and in those randomly receiving freshly thawed semen or fresh semen. The use of a vaginal device for retaining semen, the use of patient positioning, or the duration of infertility did not appear to affect the success rate. When surgically correctable pelvic disease was treated, a pregnancy rate of 22% was obtained.


Identifying constituents in commercial gasoline using Fourier transform-infrared spectroscopy and independent component analysis.
A new method is proposed that enables the identification of five refinery fractions present in commercial gasoline mixtures using infrared spectroscopic analysis. The data analysis and interpretation was carried out based on independent component analysis (ICA) and spectral similarity techniques. The FT-IR spectra of the gasoline constituents were determined using the ICA method, exclusively based on the spectra of their mixtures as a blind separation procedure, i.e. assuming unknown the spectra of the constituents. The identity of the constituents was subsequently determined using similarity measures commonly employed in spectra library searches against the spectra of the constituent components. The high correlation scores that were obtained in the identification of the constituents indicates that the developed method can be employed as a rapid and effective tool in quality control, fingerprinting or forensic applications, where gasoline constituents are suspected.


Highlighting inconsistencies regarding metal biosorption.
Thousands of articles have been devoted to examine different types of biosorbents and their use in cleaning polluted waters. An important objective of some studies has been the identification of the biosorption mechanisms. This type of investigation is not always performed, as it can only be done if scientists are aware of all mechanisms that, at least theoretically, control the removal of the target substances. Mistakes are often made, even in highly cited review articles, where biosorption mechanisms are named and/or grouped. The aim of this article is to highlight errors and inaccuracies as well as to discuss different classification systems of the biosorption mechanisms. This article serves as a guide, as well as a platform for discussion among researchers involved in the investigation of biosorbents, in an effort to avoid reproducing errors in subsequent articles.


High resolution imaging of fluorescein patterns in RCS rat retinae and their direct correlation with histology.
To assess the progressive changes in the retinal vascular bed of dystrophic and non-dystrophic Royal College of Surgeons (RCS) rats, retinae, were visualised correlating in vivo fundus fluorescein angiography (FA) with histology. FA was performed in rats aged 5 weeks to 2 years, using a Zeiss confocal scanning laser ophthalmoscope (cSLO). After the final imaging session, a subset of retinae were prepared for flat-mount histology and the vascular bed was visualised using nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) staining. While non-dystrophic rat retinae showed no substantive changes in vascular patterns with age and no demonstrable fluorescein leakage up to at least 1 year, dystrophic rat retinae showed abnormal vascular formations, demonstrable on FA and NADPH-d staining, which could be correlated in single retinae. Hyperfluorescent spots and late angiographic leakage were evident beginning at 10 weeks and progressed in severity with time: they were coincident in distribution with abnormal histological vascular complexes. The ability to monitor the same retina serially makes this approach a valuable tool for studying the dynamics of vascular change in the diseased retina, not only during the course of degeneration but also when assessing efficacy of potential therapeutic approaches.


Evaluation of a new smartphone-based digital stethoscope featuring phonocardiography and electrocardiography in dogs and cats.
This study assessed a new smartphone-based digital stethoscope (DS) featuring simultaneous phonocardiographic and one-lead electrocardiogram (ECG) recording in dogs and cats. The audio files and ECG traces obtained by the device were compared with conventional auscultation and standard ECG. A total of 99 dogs and nine cats were prospectively included. All cases underwent conventional auscultation using an acoustic stethoscope, standard six-lead ECG, standard echocardiography and recordings with the DS. All the audio recordings, phonocardiographic files and ECG traces were then blind reviewed by an expert operator. The agreement between methods was assessed using Cohen's kappa and the Bland-Altman test. Audio recordings were considered interpretable in 90% animals. Substantial agreement was found in the diagnosis of heart murmur (κ = 0.691) and gallop sound (k = 0.740). In nine animals with an echocardiographic diagnosis of heart disease, only the DS detected a heart murmur or gallop sound. ECG traces recorded with the new device were deemed interpretable in 88 % animals. Diagnosis of heart rhythm showed moderate agreement in the identification of atrial fibrillation (k = 0.596). The detection of ventricular premature complexes and bundle branch blocks revealed an almost perfect agreement (k = 1). Overall, the DS showed a good diagnostic accuracy in detecting heart murmurs, gallop sounds, ventricular premature complexes and bundle branch blocks. A clinically relevant overdiagnosis of atrial fibrillation was found but without evidence of false negatives. The DS could represent a useful screening tool for heart sound abnormalities and cardiac arrhythmias..


Exposure to human and bovine noroviruses in a birth cohort in southern India from 2002 to 2006.
Human and bovine norovirus virus-like particles were used to evaluate antibodies in Indian children at ages 6 and 36 months and their mothers. Antibodies to genogroup II viruses were acquired early and were more prevalent than antibodies to genogroup I. Low levels of IgG antibodies against bovine noroviruses indicate possible zoonotic transmission.


Healthcare inequality issues among immigrant elders after neoliberal welfare reform: empirical findings from the United States.
Even with the increasing importance being placed on research into immigrant elders' healthcare use as countries change their policies to reflect their increasing immigrant and aging populations, little research has examined changes in healthcare use disparities between immigrant and native elders in relation to these policy changes. To fill this gap in the literature, this study examined healthcare disparities in relation to the welfare reform that the US implemented in 1996 and then compared significant indicators of immigrants' healthcare use during the pre- and post-reform periods. The difference-in-difference (DD) analyses and post hoc probing of the DD analyses were used in multivariate logistic regression of the National Health Information Survey data that were pooled for the pre- and post-reform periods. The results revealed that while inequalities in healthcare existed before the reform, they significantly increased after the reform. A further test showed that the changes in the inequalities were significant among relatively long-stay immigrants, but not significant among immigrants who entered the US before the reform and thus were exempted from the reform restrictions. During the pre-reform period, insurance, employment, sex, and race/ethnicity were related to healthcare use; however, the enabling factors (i.e., insurance, income, and education) and social structural factors (i.e., marital status, family structure, length of US residency, race/ethnicity, and geographical region) explained the post-reform immigrants' healthcare use, while controlling for healthcare needs factors. These findings suggest that welfare reform may be the driving force of inequalities in healthcare.


Phenoxybenzamine in prostatic obstruction.
A short controlled trial has confirmed that phenoxybenzamine (10 or 20 mg/day) relaxes the resting proximal urethra and reduces the voiding frequency in patients with benign prostatic hypertrophy.


Determination of contact angles for three-phase flow in porous media using an energy balance.
We define contact angles, θ, during displacement of three fluid phases in a porous medium using energy balance, extending previous work on two-phase flow. We test if this theory can be applied to quantify the three contact angles and wettability order in pore-scale images of three-phase displacement. For three phases labelled 1, 2 and 3, and solid, s, using conservation of energy ignoring viscous dissipation (Δa1scosθ12-Δa12-ϕκ12ΔS1)σ12=(Δa3scosθ23+Δa23-ϕκ23ΔS3)σ23+Δa13σ13, where ϕ is the porosity, σ is the interfacial tension, a is the specific interfacial area, S is the saturation, and κ is the fluid-fluid interfacial curvature. Δ represents the change during a displacement. The third contact angle, θ13 can be found using the Bartell-Osterhof relationship. The energy balance is also extended to an arbitrary number of phases. X-ray imaging of porous media and the fluids within them, at pore-scale resolution, allows the difference terms in the energy balance equation to be measured. This enables wettability, the contact angles, to be determined for complex displacements, to characterize the behaviour, and for input into pore-scale models. Two synchrotron imaging datasets are used to illustrate the approach, comparing the flow of oil, water and gas in a water-wet and an altered-wettability limestone rock sample. We show that in the water-wet case, as expected, water (phase 1) is the most wetting phase, oil (phase 2) is intermediate wet, while gas (phase 3) is most non-wetting with effective contact angles of θ12≈48° and θ13≈44°, while θ23=0 since oil is always present in spreading layers. In contrast, for the altered-wettability case, oil is most wetting, gas is intermediate-wet, while water is most non-wetting with contact angles of θ12=134°±~10°,θ13=119°±~10°, and θ23=66°±~10°.


[Detection of T cell independent B cell maturation disorder in cocultivation studies in systemic lupus erythematosus].
Lymphocyte coculture experiments were performed in a case of monozygotic twins, discordant for SLE. Lack of responsiveness to T-cell-dependent and independent B-cell stimulation gave evidence of an intrinsic B-cell defect in the SLE twin.


Evaluating health-related quality of life as a prognostic tool for overall survival in routine cancer care for older patients with bladder cancer: A US based study.
Health-related quality of life (HRQoL) outcomes, in addition to being useful for monitoring a person's health and well-being, may also predict overall survival (OS) in cancer patients. This study's objective was to examine the association of longitudinally assessed HRQoL and OS in patients with a history of bladder cancer (BC). This longitudinal retrospective cohort study used the 1998 to 2013 Surveillance, Epidemiology and End Results database linked with Medicare Health Outcomes Survey. Study cohort included patients having HRQoL assessments both pre- and post-BC diagnosis using Short Form-36/Veterans Rand-12. Using Cox Proportional Hazards adjusted for demographics, tumor characteristics, and surgery type, we studied the associations of 3-point difference in HRQoL assessed pre- and post-BC diagnosis and change from pre-to-post diagnosis with overall survival. The study cohort included 438 BC patients with deceased patients (n = 222; 50.7%) being significantly older than those alive (77.2 vs. 75.4 years; P = 0.004). Adjusting for covariates, a 3-point difference in physical HRQoL (physical component summary [PCS]) pre-, post-, and pre-to-post BC diagnosis was associated with respectively 6.1%, 8.7%, and 7.3% (P < 0.01 for all) decreased risk of death for higher PCS. Similarly, a 3-point difference in mental HRQoL (mental component summary [MCS]) post-BC diagnosis was associated with 4.5% (P < 0.05) decreased risk of death for higher MCS. Associations between PCS/MCS and OS imply that elderly BC patients with better physical/mental health are more likely to survive longer. Monitoring HRQoL in routine cancer care would facilitate early detection of HRQoL decline and enable timely intervention by clinicians to improve OS.


Radiation therapy and combination of cladribine, cyclophosphamide, and prednisone as treatment of Bing-Neel syndrome: Case report and review of the literature.
Waldenström's macroglobulinemia is a low-grade lymphoma that produces monoclonal IgM. Central nervous system symptoms are frequent in Waldenström's macroglobulinemia, mostly associated with blood hyperviscosity. Nevertheless, central nervous system infiltration by malignant cells (Bing-Neel syndrome) has rarely been reported. We describe the case of a 72-year-old man with Waldenstrom's macroglobulinemia and central nervous system infiltration by malignant cells with tumor formation. All similar cases reported in the literature are reviewed and the different therapeutic approaches discussed.


Relationship between time of treatment of acute herpes zoster with sympathetic blockade and prevention of post-herpetic neuralgia: clinical support for a new theory of the mechanism by which sympathetic blockade provides therapeutic benefit.
Since Rosenak's original report more than 50 years ago as to the efficacy of sympathetic blocks in terminating acute herpes zoster, many investigators have reported that a more important benefit of this form of therapy is the prevention of post-herpetic neuralgia. However, most of these reports have indicated that sympathetic blocks are effective in preventing post-herpetic neuralgia only if applied soon after the onset of the acute phase of the disease; in fact, if applied too late, this form of therapy failed to prevent the development of post-herpetic neuralgia. The present study was carried out to determine more precisely the relationship between the time of treatment of acute herpes zoster and the prevention of post-herpetic neuralgia and to attempt to correlate this time with the authors' previously published theory on the mechanism by which sympathetic blocks provide the therapeutic benefit. The present study was a retrospective review of 122 patients treated at variable intervals after the onset of acute herpes zoster. Data tabulated included the duration of symptoms at the time of treatment, the number of sympathetic blocks required to provide relief, and the efficacy of the sympathetic blockade in terminating the acute phase of herpes zoster and then preventing the development of post-herpetic neuralgia. According to the data obtained in this retrospective study, sympathetic blocks terminated the pain of acute herpes zoster and prevented or relieved post-herpetic neuralgia in more than 80% of patients treated within 2 months of the onset of the acute phase of the disease, after which time the success rate decreased drastically. Sympathetic blockade applied within the first 2 months after the onset of acute herpes zoster terminated the acute phase of the disease, probably by restoring intraneural blood flow, thus preventing the death of the large fibers and avoiding the development of post-herpetic neuralgia. If sympathetic blocks were to be carried out after 2 months, the damage to the large fibers would be irreversible, and this therapeutic modality would not be able to prevent the development of post-herpetic neuralgia.


Ultrastructure and neuron-specific enolase (NSE) immunohistochemistry of Merkel cells in normal toad epidermis, and following ablation of the pars distalis of the pituitary gland.
The present study was performed in order to re-examine the possible Merkel cell dependency upon the anterior pituitary by a combined ultrastructural and NSE immunohistochemical analysis of Merkel cells in normal toads, and following pars distalis ablation. Ultrastructurally, toad Merkel cells appeared similar to those in previous reports. They were found in normal as well as in operated toads, but with lower frequency in the latter group. By NSE immunohistochemistry, Merkel cells were seen in normal toads only. Even in individual, operated toads, in which Merkel cells were found with relative high frequency by electron microscopy, no NSE could be demonstrated immunohistochemically. It is discussed whether the amount of NSE present depends upon the physiological state of the Merkel cell and in some cells occurs in so low an amount that the NSE antigen cannot be detected by the immunocytochemical method applied. If it is so, the failure to demonstrate Merkel cells in the operated toads by means of the specific marker NSE may be interpreted as an inhibition of NSE expression following pars distalis ablation. This interpretation combined with the lower number of Merkel cells found ultrastructurally in operated toads support a previous indication of an influence of the anterior pituitary--directly or indirectly--upon toad Merkel cell function.


Contractures and increase in internal longitudianl resistance of cow ventricular muscle induced by hypoxia.
This study was performed to determine whether hypoxia in glucose-free solutions can increase the electrical resistance of intercellular junctions in ventricular muscle. Internal longitudinal resistance (Ri), mechanical tension, and transmembrane action potentials were measured simultaneously in cow ventricular trabeculae. The mean control value of Ri was 265 +/- 38 omegacm (mean +/- SE) at 34 degrees C. After 1 hour of hypoxia in glucose-free Tyrode's solution, it had increased by 300 +/- 41% (n = 11, P less than 0.001). The rise in Ri was closely related to the increase in resting tension (contracture). These effects were more pronounced during a second exposure to hypoxia and were potentiated by application of epinephrine, by increasing extracellular calcium concentration, and by increasing frequency of stimulation. Addition of glucose (50 mM) provided some protection against hypoxia. It is inferred that the increase in Ri is entirely due to the increase in the resistance of intercellular junctions (electrical uncoupling). Intracellular calcium may be responsible for both the contracture and the uncoupling.


Fetomaternal outcome among women with mitral stenosis after balloon mitral valvotomy.
To compare pregnancy outcomes among patients with non-operated mitral stenosis and those who had balloon mitral valvotomy before pregnancy. In a study at a tertiary-care referral hospital in Kolkata, India, 48 women with mitral stenosis who delivered between July 2007 and June 2008 were separated into 2 groups according to whether they had cardiac surgery before pregnancy. Eighteen women in the test group had balloon mitral valvotomy before pregnancy, whereas 30 women in the control group had no cardiac surgery. Fetomaternal outcomes were compared between the 2 groups. In the control group, significantly more patients had palpitations (P=0.032) and severe dyspnea (P=0.017) than in the test group. The incidence of preterm labor in the test group (1/18) was lower than that in the control group (10/30) (P=0.035). However, the groups did not differ in mode of delivery, mean birth weight, or neonatal complications. Balloon mitral valvotomy improved maternal symptoms and should be done to prevent maternal morbidity and to reduce the incidence and complications of preterm labor.


The effect of normalization of sodium on bone turnover markers in patients with epilepsy. A randomized single-blinded placebo-controlled trial.
Hyponatremia [p[Na]<136 mmol/L] is an independent risk factor for decreased bone mineral density (BMD). However, whether hyponatremia represents a surrogate marker, or a direct causal relationship to bone loss remains unknown. The aim of the study was to investigate the effect of salt replacement therapy on bone turnover markers (BTM) and BMD in patients with epilepsy and chronic hyponatremia. This prospective single-blinded randomized trial investigated serum BTM and BMD, evaluated by Dual Energy X-ray Absorptiometry (DXA), in 21 patients at baseline and following three months of salt replacement therapy. Patients with two consecutive measurements of hyponatremia prior to baseline and no known osteoporosis were included from the epilepsy out-patient clinic at Rigshospitalet, Denmark. Seven patients were randomized to placebo and 14 to salt intervention. The baseline p[Na] was 134 (130.5-140) mmol/L (median (IQR)). All patients had BTM within age-specific reference ranges at baseline. Following 3 months of intervention with 3-9 g of salt daily there was no difference in levels of procollagen type 1 N-terminal propeptide (P1NP) or C-terminal cross-linking telopeptide of type 1 collagen (CTX) between placebo and intervention. Nor was there any difference in BMD evaluated at the lumbar spine (L1-L4) or at the femoral neck or total hip. In our study, salt replacement did neither affect BTM nor BMD. However, due to the small size of the study, more studies are needed to further investigate this.


The relation of iron status and hemochromatosis gene mutations in patients with chronic hepatitis C.
Elevated hepatic iron concentration may affect the response to antiviral therapy in chronic hepatitis C. This study explored the contribution of genetic hemochromatosis to iron accumulation in chronic hepatitis C. HFE mutations (C282Y and H63D) were assessed in 184 patients with chronic hepatitis C virus and 487 controls. Liver biopsy specimens were available in 149 patients. Hepatic iron content was measured in 114 patients by atom-absorption spectrophotometry. The C282Y and H63D allele frequencies were 7.06 and 11.6 in patients and 4.83 and 11.09 in controls, respectively. Eight patients were homozygotes (5 C282Y [2.7%] and 3 H63D [1.6%]), 2 compound heterozygotes (1%), and 49 heterozygotes (14 C282Y [7.6%] and 35 H63D [19%]). Biochemical evidence of iron overload was more common in patients with HFE mutations (28 of 47) than in those without (34 of 102; P = 0.0045). Histological iron grading and hepatic iron content overlapped among patients with or without mutations. A hepatic iron index of >1.9 was observed only in 1 of the 4 C282Y homozygotes and 1 of the 3 H63D homozygotes. HFE mutations contribute to but do not fully explain hepatic iron accumulation in chronic hepatitis C. Furthermore, C282Y or H63D homozygosity in chronic hepatitis C is not necessarily associated with a high hepatic iron content.


Preparation of Structure Vacancy Defect Modified Diatomic-Layered g-C3 N4 Nanosheet with Enhanced Photocatalytic Performance.
Structure self-modification of graphitic carbon nitride (g-C3 N4 ) without the assistance of other species has attracted considerable attention. In this study, the structure vacancy defect modified diatomic-layered g-C3 N4 nanosheet (VCN) is synthesized by thermal treatment of bulk g-C3 N4 in a quartz tube with vacuum atmosphere that will generate a pressure-thermal dual driving force to boost the exfoliation and formation of structure vacancy for g-C3 N4 . The as-prepared VCN possesses a large specific surface area with a rich pore structure to provide more active centers for catalytic reactions. Furthermore, the as-formed special defect level in VCN sample can generate a higher exciton density at photoexcitation stage. Meanwhile, the photogenerated charges will rapidly transfer to VCN surface due to the greatly shortened transfer path resulting from the ultrathin structure (≈1.5 nm), which corresponds to two graphite carbon nitride atomic layers. In addition, the defect level alleviates the drawback of enlarged bandgap caused by the quantum size effect of nano-scaled g-C3 N4 , resulting in a well visible-light utilization. As a result, the VCN sample exhibits an excellent photocatalytic performance both in hydrogen production and photodegradation of typical antibiotics.


Percutaneous contrast-enhanced ultrasound-guided transabdominal sac embolization is an effective technique for treating complicated type II endoleaks after endovascular aneurysm repair.
In the present study, we evaluated and compared the outcomes of transarterial embolization with those of percutaneous contrast-enhanced ultrasound-guided transabdominal sac embolization (PUSE) for type II endoleaks (T2ELs). A retrospective review was conducted of consecutive patients who had undergone T2EL embolization between January 2015 and December 2020 at our center. The cohort was divided into two groups according to the embolization approach: PUSE vs transarterial. Freedom from aneurysm growth, safety, immediate technical success, freedom from persistent T2ELs, and the repeat embolization rate were assessed. A total of 25 patients and 28 embolization procedures (PUSE, n = 16; transarterial embolization, n = 12) were examined. Both the fluoroscopic time (13.3 ± 3.2 minutes vs 35.0 ± 7.0 minutes; P < .001) and the procedural time (84.9 ± 8.4 minutes vs 117.1 ± 14.8 minutes; P < .001) were significantly shorter in the PUSE group than in the transarterial group. After the embolization procedure, the patients were followed up for a mean duration of 24.7 ± 14.9 months for the PUSE group and 35.9 ± 21.1 months for the transarterial group (P = .1323). Five patients in the transarterial group had undergone unsuccessful embolization, with success in 7 of the 12 patients in the transarterial group and all 16 patients in the PUSE group (P = .0081). Failure had resulted from failed transarterial access or a recurrent T2EL. Three of the five patients had undergone subsequent PUSE during follow-up. No patient in the PUSE group had experienced sac expansion compared with four patients in the transarterial group (P = .0242). Similarly, no patient in the PUSE group had developed a newly discovered T2EL vs four patients in the transarterial group (P = .0242). Thus, the outcomes were markedly better for the PUSE group than were those for the transarterial group. A major procedure-related complication (abdominal abscess) occurred in one patient in the transarterial group. PUSE is safe and effective for managing T2ELs. It yields better outcomes in terms of preventing aneurysm growth, decreasing the incidence of repeat embolization and complications, minimizing the recurrence of T2ELs, and reducing the fluoroscopic and procedural times. We, thus, regard it as the preferred approach for the management of T2ELs.


Correction: A Historical Overview of the Classification, Evolution, and Dispersion of Leishmania Parasites and Sandflies.
[This corrects the article DOI: 10.1371/journal.pntd.0004349.].


Graphene oxide-based colorimetric/fluorescence dual-mode immunochromatography assay for simultaneous ultrasensitive detection of respiratory virus and bacteria in complex samples.
A point-of-care testing biosensor that supports direct, sensitive, and simultaneous identification of bacteria and virus is still lacking. In this study, an ultrasensitive immunochromatography assay (ICA) with colorimetric/fluorescence dual-signal output was proposed for flexible and accurate detection of respiratory virus and bacteria in complex samples. Colorimetric AuNPs of 16 nm and two layers of quantum dots (QDs) were coated onto the surface of monolayer graphene oxide (GO) layer by layer to form a multilayered dual-signal nanofilm. This material not only can generate strong colorimetric and fluorescence signals for ICA analysis but also can provide larger surface area, better stability, and superior dispersibility than conventional spherical nanomaterials. Two test lines were built onto the ICA strip to simultaneously detect common respiratory virus influenza A and respiratory bacteria Streptococcus pneumoniae. The dual-signal mode of assay greatly broadened the applied range of ICA method, in which the colorimetric mode allows for quick determination of virus/bacteria and the fluorescence mode ensures the highly sensitive and quantitative detection of target pathogens with detection limits down to 891 copies/mL and 17 cells/mL, respectively. The proposed dual-mode ICA can also be applied directly for real biological and environment samples, which suggests its great potential for field application.


Evaluating keloid recurrence after surgical excision with prospective longitudinal scar assessment scales.
Evaluation tools are used to quantify scar evolution and determine treatment effectiveness. In clinical practice, scar assessment scales are less costly, tend to cover a greater number of aspects related to scar characteristics and can incorporate a patient's opinion in the assessment. However, the scales have not yet been used as an evaluation method for the postoperative recurrence of keloids. The study aims to evaluate the effectiveness of scar rating scales for keloid recurrence after surgical excision. Patients (n = 25) with keloids on the trunk were treated by surgical resection and postoperative beta radiation therapy. On the 3rd, 6th, 9th and 12th postoperative months, two specialists classified the lesions qualitatively in recurrent and non-recurrent cases. Furthermore, in the objective evaluation, the items on the Seattle Scar Scale (SSS) and the Stony Brook Scar Evaluation Scale (SBSES) were assessed by specialists, and the patients assessed items on the Patient Scar Assessment Scale (PSAS) for the pre- and postoperative periods. The scars were classified qualitatively as "good" or "poor." Recurrence was observed in 18 patients (72%), according to the specialists' qualitative assessments. The best scores on the SSS and SBSES were given to the non-recurrent (p < 0.001) scars. The highest PSAS values were for the scars classified as "poor" (p < 0.001). There were no differences in the PSAS values for the preoperative period and outcomes for the recurrent scars (p = 0.519). The outcomes showed that the non-recurrent scars had lower values on the PSAS compared to the recurrent scars (p = 0.001) and compared to the preoperative period (p = 0.004). The PSAS, SSS and SBSES scales were effective methods in distinguishing keloid postoperative recurrence. It is necessary to establish the recurrence cut-off scores for each of the scales according to the treatment used.


Antibacterial, antifungal and antimycobacterial activities of some pyrazoline, hydrazone and chalcone derivatives.
Twenty-seven previously reported chalcones and their pyrazoline and hydrazone derivatives as well as two further chalcones have been screened for their antimicrobial, antifungal and antimycobacterial activities against standard microbial strains and drug resistant isolates. The minimum inhibitory concentration (MIC) value of each compound was determined by a two-fold serial microdilution technique. The compounds were found to possess a broad spectrum of antimicrobial activities with MIC values of 8-128 μg/mL. One compound [(E)-1-(4-hydroxyphenyl)-3-p-tolylprop-2-en-1-one] had equal activity with gentamycin (8 μg/mL) against Enterococcus faecalis. Chalcones were found to be more active than their hydrazone and 2-pyrazoline derivatives against Staphylococcus aureus ATCC 29213 and E. faecalis ATCC 29212.


Antibiotic resistance in bloodstream isolates from high-complexity paediatric units in Madrid, Spain: 2013-2021.
Antimicrobial resistance (AMR) has become a significant challenge in high-complexity healthcare settings. To evaluate the prevalence of AMR in bloodstream isolates from high-complexity paediatric units in Spain over a nine-year period. A retrospective observational multicentre study was conducted in three tertiary hospitals, analysing bloodstream isolates from patients aged <18 years admitted to the paediatric intensive care, neonatology, and oncology-haematology units between 2013 and 2021. Demographics, antimicrobial susceptibility, and resistance mechanisms were analysed in two periods (2013-2017 and 2017-2021). In all, 1255 isolates were included. AMR was more prevalent in older patients and those admitted to the oncology-haematology unit. Multidrug resistance was observed in 9.9% of Gram-negative bacteria (GNB); 20.0% of P. aeruginosa vs 8.6% of Entero-bacterales (P < 0.001), with an increase in Enterobacterales from 6.2% to 11.0% between the first and the second period (P = 0.021). Difficult-to-treat resistance was observed in 2.7% of GNB; 7.4% of P. aeruginosa vs 1.6% of Enterobacterales (P < 0.001), with an increasing trend in Enterobacterales from 0.8% to 2.5% (P = 0.076). Carbapenem resistance among Enterobacterales increased from 3.5% to 7.2% (P = 0.029), with 3.3% producing carbapenemases (67.9% VIM). Meticillin resistance was observed in 11.0% of S. aureus and vancomycin resistance in 1.4% of Enterococcus spp., with both rates remaining stable throughout the study period. This study reveals a high prevalence of AMR in high-complexity paediatric units. Enterobacterales showed a concerning increasing trend in resistant strains, with higher rates among older patients and those admitted to oncology-haematology units.


Remotely Produced and Axon-Derived Netrin-1 Instructs GABAergic Neuron Migration and Dopaminergic Substantia Nigra Development.
The midbrain dopamine (mDA) system is composed of molecularly and functionally distinct neuron subtypes that mediate specific behaviors and show select disease vulnerability, including in Parkinson's disease. Despite progress in identifying mDA neuron subtypes, how these neuronal subsets develop and organize into functional brain structures remains poorly understood. Here we generate and use an intersectional genetic platform, Pitx3-ITC, to dissect the mechanisms of substantia nigra (SN) development and implicate the guidance molecule Netrin-1 in the migration and positioning of mDA neuron subtypes in the SN. Unexpectedly, we show that Netrin-1, produced in the forebrain and provided to the midbrain through axon projections, instructs the migration of GABAergic neurons into the ventral SN. This migration is required to confine mDA neurons to the dorsal SN. These data demonstrate that neuron migration can be controlled by remotely produced and axon-derived secreted guidance cues, a principle that is likely to apply more generally.


Prevalence of Celiac Disease in Patients with Autoimmune Thyroid Disease: A Meta-Analysis.
Several screening studies have indicated an increased prevalence of celiac disease (CD) among individuals with autoimmune thyroid disease (ATD), but estimates have varied substantially. The aim of this study was to examine the prevalence of CD in patients with ATD. A systematic review was conducted of articles published in PubMed Medline or EMBASE until September 2015. Non-English papers with English-language abstracts were also included, as were research abstracts without full text available when relevant data were included in the abstract. Search terms included "celiac disease" combined with "hypothyroidism" or "hyperthyroidism" or "thyroid disease." Fixed-effects inverse variance-weighted models were used. Meta-regression was used to examine heterogeneity in subgroups. A pooled analysis, based on 6024 ATD patients, found a prevalence of biopsy-confirmed CD of 1.6% [confidence interval (CI) 1.3-1.9%]. Heterogeneity was large (I(2) = 70.7%). The prevalence was higher in children with ATD (6.2% [CI 4.0-8.4%]) than it was in adults (2.7%) or in studies examining both adults and children (1.0%). CD was also more prevalent in hyperthyroidism (2.6% [CI 0.7-4.4%]) than it was in hypothyroidism (1.4% [CI 1.0-1.9%]). About 1/62 patients with ATD have biopsy-verified CD. It is argued that patients with ATD should be screened for CD, given this increased prevalence.


Developing an administrative plan for transfusion medicine--a global perspective.
Throughout the world blood services aim to provide a life-saving service by ensuring an adequate supply of safe blood. However, across the world blood services are at very different levels of development. Consequently, the actions taken in one country or region would not be appropriate in another. This paper aims to identify how suitable solutions can be developed to match the different prevailing circumstances of an individual country or region. In trying to do this it is important to look at the whole of the supply chain within a blood service and identify the part where a change could make the biggest impact. Four key areas are identified that are integral to this. These are the donor, testing of blood, hemovigilance, and overall management arrangements. Whilst the first two have largely been addressed in highly developed countries, there is still much work that could be done in these areas in developing countries. In particular, a move to voluntary nonremunerated donors worldwide would significantly improve overall safety. Hemovigilance systems are identified as a powerful tool to influence policy development, yet these are largely under developed throughout the world. In order to make high impact and sustainable changes it is important that those in the blood industry across the world work together to improve education and training, to share experience of best practice, and to move to develop agreed standards in transfusion medicine. It is imperative that developed countries recognize the importance of working with developing countries if the safety of the global blood supply is to be maintained and improved.


Safe(r) by design guidelines for the nanotechnology industry.
Expectations for safer and sustainable chemicals and products are growing to comply with the United Nations and European strategies for sustainability. The application of Safe(r) by Design (SbD) in nanotechnology implies an iterative process where functionality, human health and safety, environmental and economic impact and cost are assessed and balanced as early as possible in the innovation process and updated at each step. The EU H2020 NanoReg2 project was the first European project to implement SbD in six companies handling and/or manufacturing nanomaterials (NMs) and nano-enabled products (NEP). The results from this experience have been used to develop these guidelines on the practical application of SbD. The SbD approach foresees the identification, estimation, and reduction of human and environmental risks as early as possible in the development of a NM or NEP, and it is based on three pillars: (i) safer NMs and NEP; (ii) safer use and end of life and (iii) safer industrial production. The presented guidelines include a set of information and tools that will help deciding at each step of the innovation process whether to continue, apply SbD measures or carry out further tests to reduce uncertainty. It does not intend to be a prescriptive protocol where all suggested steps have to be followed to achieve a SbD NM/NEP or process. Rather, the guidelines are designed to identify risks at an early state and information to be considered to identify those risks. Each company adapts the approach to its specific needs and circumstances as company decisions influence the way forward.


MiR-25 suppresses 3T3-L1 adipogenesis by directly targeting KLF4 and C/EBPα.
In the past decade, miRNA emerges as a vital player in orchestrating gene regulation and maintaining cellular homeostasis. It is well documented that miRNA influences a variety of biological events, including embryogenesis, cell fate decision, and cellular differentiation. Adipogenesis is an organized process of cellular differentiation by which pre-adipocytes differentiate towards mature adipocytes. It has been shown that adipogenesis is tightly modulated by a number of transcription factors such as PPARγ, KLF4, and C/EBPα. However, the molecular mechanisms underlying the missing link between miRNA and adipogenesis-related transcription factors remain elusive. In this study, we unveiled that miR-25, a member of miR-106b-25 cluster, was remarkably downregulated during 3T3-L1 adipogenesis. Restored expression of miR-25 significantly impaired 3T3-L1 adipogenesis and downregulated the expression of serial adipogenesis-related genes. Further experiments presented that ectopic expression of miR-25 did not affect cell proliferation and cell cycle progression. Finally, KLF4 and C/EBPα, two key regulators of adipocyte differentiation, were experimentally identified as bona fide targets for miR-25. These data indicate that miR-25 is a novel negative regulator of adipocyte differentiation and it suppressed 3T3-L1 adipogenesis by targeting KLF4 and C/EBPα, which provides novel insights into the molecular mechanism of miRNA-mediated cellular differentiation.


Emotion regulation and aggressive behavior in preschoolers: the mediating role of social information processing.
This study examined whether the relation between maladaptive emotion regulation and aggression was mediated by deviant social information processing (SIP). Participants were 193 preschool children. Emotion regulation and aggression were rated by teachers. Deviant SIP (i.e., attribution of hostile intent, aggressive response generation, aggressive response evaluation and decision) was measured from children's responses to hypothetical social conflicts. Findings revealed that the relation between maladaptive emotion regulation and aggression was direct and not mediated by SIP biases (i.e., aggressive response generation, aggressive response evaluation and decision). Results are discussed from a theoretical and methodological perspective.


The automated assessment of the effect of flurazepam and nitrazepam on mood state.
Some further results on the effects of the two hypnotic drugs, nitrazepam and flurazepam monohydrochloride, on mood state are described. An automated assessment and scoring system, Computer Assisted Psychometric System (C.A.P.S.), was used to assess mood state and showed that both hypnotics had a mild euphoriant effect even when administered to healthy volunteers during the daytime. This was most marked in the case of nitrazepam. It is argued that such euphoriant side effects should be further investigated as they can occur when hypnotics are administered on a long-term nightly basis, and there may therefore be a dependency aspect for those patients who habitually take such hypnotic drugs. The broad scope of the C.A.P.S. system is also discussed.


A general and concise asymmetric synthesis of sphingosine, safingol and phytosphingosines via tethered aminohydroxylation.
A novel, practical and efficient enantioselective synthesis of sphingoid bases, l-threo-[2S,3S]-sphinganine (safingol), l-threo-[2S,3S]-sphingosine, l-arabino-[2R,3S,4R] and l-xylo-[2R,3S,4S]-C(18)-phytosphingosine is described. The synthetic strategy features the Sharpless kinetic resolution and tethered aminohydroxylation (TA) as the key steps.


Critical role of the hippocampus in memory for sequences of events.
Recent models of hippocampal function emphasize the potential role of this brain structure in encoding and retrieving sequences of events that compose episodic memories. Here we show that hippocampal lesions produce a severe and selective impairment in the capacity of rats to remember the sequential ordering of a series of odors, despite an intact capacity to recognize odors that recently occurred. These findings support the hypothesis that hippocampal networks mediate associations between sequential events that constitute elements of an episodic memory.


[Development and application of an "IR-spectrophotometer-minicomputer" system for determination of steroid hormones in patients with malignant neoplasms].
An automated IR-spectrophotometer-mini-computer system was designed for assay of steroid hormone level. Its application obviates a clinical analysis of urine. The ratio of 17-ketogenic steroids to androsterone was found to be significantly higher in patients with lung cancer than in healthy controls. The system may be used for identification of groups at high risk both during screenings and in oncological clinic.


A selective difference between human Y-chromosomal DNA haplotypes.
DNA analysis is making a valuable contribution to the understanding of human evolution [1]. Much attention has focused on mitochondrial DNA (mtDNA) [2] and the Y chromosome [3] [4], both of which escape recombination and so provide information on maternal and paternal lineages, respectively. It is often assumed that the polymorphisms observed at loci on mtDNA and the Y chromosome are selectively neutral and, therefore, that existing patterns of molecular variation can be used to deduce the histories of populations in terms of drift, population movements, and cultural practices. The coalescence of the molecular phylogenies of mtDNA and the Y chromosome to recent common ancestors in Africa [5] [6], for example, has been taken to reflect a recent origin of modern human populations in Africa. An alternative explanation, though, could be the recent selective spread of mtDNA and Y chromosome haplotypes from Africa in a population with a more complex history [7]. It is therefore important to establish whether there are selective differences between classes (haplotypes) of mtDNA and Y chromosomes and, if so, whether these differences could have been sufficient to influence the distributions of haplotypes in existing populations. A precedent for this hypothesis has been established for mtDNA in that one mtDNA background increases susceptibility to Leber hereditary optic neuropathy [8]. Although studies of nucleotide diversity in global samples of Y chromosomes have suggested an absence of recent selective sweeps or bottlenecks [9], selection may, in principle, be very important for the Y chromosome because it carries several loci affecting male fertility [10] [11] and as many as 5% of males are infertile [11] [12]. Here, we show that one class of infertile males, PRKX/PRKY translocation XX males, arises predominantly on a particular Y haplotypic background. Selection is, therefore, acting on Y haplotype distributions in the population.


Personal immune profiles: Diversity and prognostic value for oral tongue squamous cell carcinoma evaluated by comprehensive immune parameter analyses with multiplex immunofluorescence.
Understanding the tumor immune microenvironment is becoming increasingly necessary for risk prediction and treatment selection. In particular, oral cancer has various immunosuppressive characteristics in the tumor microenvironment. Therefore, we comprehensively assessed the immune profiles of oral tongue squamous cell carcinoma (OTSCC). Multiplex immunofluorescence and tissue imaging analyses were performed to evaluate immune profiles at the invasive tumor front of 60 OTSCC surgical specimens. We analyzed 58 immune parameters including the density and proportion (%) of total leukocytes (Leu) and T cells, six subsets of T and myeloid cells, and the expression of programmed cell death-1 (PD-1) and PD-1 ligand 1 (PD-L1). The density, proportion, and location of CD45+ Leu, three T cell subsets (CD8+, Foxp3-CD4+ conventional, and Foxp3+CD4+ regulatory T cells), CD163-CD68+ M1 and CD163+CD68+ M2 macrophages, and neutrophils were highly variable at the individual level. The density and proportion of M2 macrophages were significantly lower in the T1 stage group. Risk prediction analyses for recurrence and/or metastasis (R/M) showed that R/M (+) T1 cases had significantly higher M2 density and percentages. The immune profiles of OTSCC patients are diverse and cannot be predicted from clinicopathological information alone. The M2 macrophage abundance is a potential candidate biomarker for R/M in the early stage of OTSCC. Personal immune profiling may provide beneficial information for risk prediction and treatment selection.


Vitamin D Supplementation in Childhood - A Review of Guidelines.
Vitamin D, a unique vitamin with endocrine function is required in the human body primarily for calcium homeostasis and possibly several other functions. Deficiency of the vitamin is extremely frequent world-wide. Studies on Indian population place the prevalence of deficiency at 70 to 100% in healthy individuals. There are several guidelines available on definition of vitamin D deficiency and supplementation in healthy children and adults. Sufficiency or deficiency of the vitamin depend upon the levels of 25OHD and various cut-offs are suggested by different groups formulating the guidelines. Although the vitamin is synthesized in the skin with the help of sunlight, it is mostly agreed by various groups that oral supplementation must be done in infants and in certain high risk groups. No such formal guidelines currently exist for Indian children though there is a need to develop one.


Interventional radiologic treatment of complications following gastric bypass surgery for morbid obesity.
Complications of gastric bypass surgery include leakage from the gastrojejunal anastomosis with abscess formation and anastomotic stenosis. Using interventional radiologic techniques, we have treated 18 patients with such complications following surgery for morbid obesity, with clinical success in 11. Procedures included 9 abdominal abscess drainages and 7 balloon dilatations of stenotic or occluded gastrojejunal anastomoses. Eight of 9 abscesses resolved completely; 3 of 7 balloon dilatations resulted in long-term clinical improvement. We describe the techniques used as well as problems encountered in these patients.


Sensitivity of smooth eye movement to small differences in target velocity.
The precision of smooth pursuit eye movements was described by means of a new dependent measure, the "oculomotor difference threshold" (analogous to the perceptual difference threshold) which represents the smallest difference in target velocity that produces statistically distinguishable differences in eye velocity. Oculomotor difference thresholds for constant velocity motions were largest (greater than 50% of target velocity) during the initial 200 msec of target motion, despite fairly high average gains (0.7-1.4) during the same period. Oculomotor difference thresholds declined over time. By about 600-700 msec after the onset of target motion they reached values as low as the perceptual difference thresholds measured psychophysically with the same target velocities. The similarity of the difference thresholds suggests that equally precise sensory representations of target velocity influenced perception and smooth eye movements. Nonsensory influences on smooth eye movement were also found. Smooth pursuit velocity: (1) depended on the velocity of targets in preceding trials; (2) was decreased during the initial 200 msec of target motion when the duration of motion was reduced from 1 sec to 200 msec, a result which shows that high initial pursuit velocity depends on the expectation that pursuit will continue. These effects of context and expected duration allowed the eye to achieve quickly a velocity close to that of the target it was most likely to encounter. Study of the precision of pursuit may be valuable for characterizing its sensory input, but study of the effects of the context in which a stimulus appears and the effects of expectations about future target motion may be more valuable for understanding how smooth eye movements guarantee retinal image velocities optimal for vision.


Evaluation of the bisphenol released in the saliva after residual adhesive removal in orthodontic patients by using ultrasonic scaling and rotary system: A single-center randomized clinical trial.
Bisphenol A (BPA) is a substance commonly used in dental materials with noxious properties. Monomers of this substance may be dissolved in the saliva and cause adverse effects. This study aimed to evaluate the amount of BPA released in the saliva after residual adhesive removal in orthodontic patients using an ultrasonic scaler (US) and tungsten carbide bur (TCB). This single-center randomized clinical trial was conducted on 40 subjects whose stainless-steel brackets were bonded directly with light-cured bonding and composite. The subjects were randomly divided into 2 equal groups (n = 20) of TCB or US according to the adhesive removal method. The salivary BPA level was determined using high-performance liquid chromatography-mass spectrometry. And adhesive cleaning time was measured by a stopwatch. Data were analyzed by SPSS using an independent t test and paired-samples t test (P <0.05). The mean salivary BPA level was significantly lower in the TCB method than in the US method. (1.008 ± 0.061 μg/mL and 2.83 ± 0.24 μg/mL, respectively) (P <0.001). The mean adhesive cleanup time was significantly shorter in the TCB method than in the US method (8.86 ± 0.83 minutes and 13.20±1.02 minutes, respectively) (P <0.001). According to the results, residual adhesive removal with TCB released less BPA in saliva and shortened the adhesive cleaning time than the US method. The trial was registered at the Iranian Registry of Clinical Trials (IRCT20200702047988N1). The protocol was not published before trial commencement.


Stabilization of U(III) to Oxidation and Hydrolysis by Encapsulation Using 2.2.2-Cryptand.
The electrochemical properties of U(III)-in-crypt (crypt = 2.2.2-cryptand) were examined in dimethylformamide (DMF) and acetonitrile (MeCN) to determine the oxidative stability offered by crypt as a ligand. Cyclic voltammetry revealed a U(III)/U(IV) irreversible oxidation at EPA= -0.49 V (vs Fe(C5H5)2+/0) in DMF and at EPA= -0.31 V (vs Fe(C5H5)2+/0) in MeCN. The electrochemistry of U(III)-in-crypt complexes in the presence of water was also examined. These studies are supported by crystallographically characterized examples of U(III)-in-crypt complexes as DMF, MeCN, and water adducts.


Overweight, obesity and work functioning: the role of working-time arrangements.
Obesity is associated with productivity loss, but little is known about how obese workers function at work and also the role of working-time arrangements on this association is lacking. Therefore, the aim of this study was to examine the association of overweight and obesity with work functioning (WF), and to determine whether the associations differ between workers with different working-time arrangements. A cross-sectional study was conducted within the sampling frame of the 'Shift Your Work' study that examined the effect of irregular working-times in relation to health and functioning at work. We included N = 622 Dutch employees, of which N = 384 (62%) were shift-workers, N = 171 (27%) on-call workers and N = 67 (11%) day-workers. Overweight and obesity were defined as BMI 25-30 and ≥30, respectively. WF was assessed using the Work-Role Functioning Questionnaire. The prevalences of overweight and obesity were 48% and 10% in all workers, 49% and 11% in shift-workers, 45% and 10% in on-call workers, and 49% and 6% in day workers, respectively. In all workers, obesity was associated with lower WF scores for physical demands (adjusted estimate, aB = -5.5). In shift-workers, obesity was associated with lower WF scores for output and physical demands (aB = -8.8 and -6.8, respectively). In day and on-call workers, overweight and obesity were not associated with WF. Overweight and obesity are highly prevalent in the working population. Obesity might reduce the executive function performance beyond physical limitations, and limit the ability to accomplish tasks successfully, especially in shift workers.


Relation of heart failure hospitalization to exposure to fine particulate air pollution.
Cardiopulmonary disease has been associated with particulate matter (PM) air pollution. There is evidence that exposure to elevated PM concentrations increases risk of acute ischemic heart disease events, alters cardiac autonomic function, and increases risk of arrhythmias. It is plausible, therefore, that PM exposure may exacerbate heart failure (HF). A case-crossover study design was used to explore associations between fine PM (PM(2.5): particles with an aerodynamic diameter < or =2.5 microm) and 2,628 HF hospitalizations. Patients lived on Utah's Wasatch Front and were drawn from those hospitalized at Intermountain Healthcare facilities with a primary diagnosis of HF. A 14-day lagged cumulative moving average of 10 microg/m(3) PM(2.5) was associated with a 13.1% (95% confidence interval 1.3 to 26.2) increase in HF admissions. The strongest PM(2.5)-HF associations were for elderly patients who had previously been admitted for HF and who required only a short period of hospitalization. HF hospitalizations are associated with lagged cumulative exposure to PM(2.5) of approximately 2 weeks. In conclusion, particulate air pollution may play a role in precipitating acute cardiac decompensation in otherwise well-managed patients with HF, perhaps through effects of PM on myocardial ischemia, cardiac autonomic function, and/or arrhythmic effects.


Ergonomics considerations in hand and wrist tendinitis.
The objectives of this article are to present (1) a historical perspective on hand and wrist tendinitis in workers, (2) new data that demonstrate a relationship between the repetitiveness and forcefulness of manual work and the prevalence of tendinitis, (3) possible biomechanical factors in tendinitis, and (4) possible job modifications for the prevention of tendinitis. Numerous studies during the last 100 years show that tendinitis is a major cause of worker suffering and workers' compensation in intensive hand work. Epidemiologic data show that the risk of hand and wrist tendinitis in persons who perform highly repetitive and forceful jobs is 29 times greater than in persons who perform jobs that are low in repetitiveness and force. A possible factor in this relationship is viscous deformation of the tendons and adjacent tissues. Although these data suggest that the risk of tendinitis among workers can be reduced by reduction of the repetitiveness and the forcefulness of the work, this hypothesis has not yet been fully tested.


Correlations between age, biomedical variables, and cognition in patients with schizophrenia.
To illustrate the influence of clinical variables on cognition performance in patients with schizophrenia (SCZ). Using the 66nao Brain Training device (a novel measurement tool), the cognitive performance of 99 patients with SCZ was evaluated. Patients were diagnosed by the ICD-10 diagnostic criteria for SCZ, and their age were 16-68 years old. Furthermore, we explored the relationship between age, biomedical variables and specific cognitive domains in patients with SCZ. Patients were divided into two groups: various of cognitive domains impairment group and non-impairment group according to the norm scores. All data were analyzed using RStudio Version 1.0.44 (RStudio, Inc.). Patients with SCZ had obvious cognitive impairment in total and five subdomains of cognitive function. We found that 1) SCZ patients with impaired cognitive total score experienced significant older age and longer illness duration compared with those with normal cognitive total score. 2) SCZ patients with impaired memory experienced significant older age compared with those with normal memory. 3) SCZ patients with impaired attention showed significant lower serum triglyceride (TG) level compared with those with normal attention. 4) SCZ patients with impaired flexibility performed significant longer illness duration compared with those with normal flexibility. 5) SCZ patients with impaired cognitive agility performed significant older age, longer duration, and higher systolic blood pressure (SBP) compared with those with normal cognitive agility. 6) The age, illness duration and SBP in patients with impaired time perception were marginally different from those of subjects with normal time perception. There are five dimensions (memory, attention, flexibility, cognitive agility, and time perception) of cognitive dysfunction in SCZ patients. Age, illness duration, TG, and SBP might play vital roles in various subdomains of the cognitive deficits respectively in patients with SCZ.


Isometric non-machine-based prevention training program: effects on the cross-sectional area of the paravertebral muscles on magnetic resonance imaging.
The purpose of this study was to determine potential effects of isometric non-machine-based training on the cross-sectional area (CSA) of the paravertebral muscles in volunteers who were participants in a prevention program. An increase in the CSA of back muscles after various machine-based exercises have been reported but non-machine-based training programs have not been adressed before. In the study 14 volunteers, who were participants of a company internal prevention program, underwent a magnetic resonance (MR) examination before and after a 3 months training program to improve back muscle strength. The MRI protocol consisted of T1-weighted and T2-weighted images aligned to the intervertebral disc spaces. The CSAs of the erector spinae and quadratus lumborum muscles were assessed twice by 2 operators at the levels L3/4, L4/5 and L5/S1. Out of 14 subjects 11 completed the training. The recorded CSA values exhibited an intrarater and intrarater correlation coefficient ranging from 0.949 to 0.989. There was an increase in CSA in all subjects after the training period (mean increase 8%). A 3-month isometric training program is sufficient to effect measurable increases in back muscles volume. The study demonstrated the usefulness of MRI to quantify such changes as a measure of training efficacy and compliance into the training program. These results represent a rationale for further studies to determine the effect of different training methods on the CSA of back muscles and to correlate structural changes with clinical symptoms in chronic low back pain syndrome.


Expression of nerve growth factor-like polypeptides and immunoreactivity related to the two types of neurotrophin receptors in earthworm tissues.
Nerve growth factor (NGF) belongs by sequence homology to the neurotrophins, a family of proteins binding the same p75 receptor and closely related members of the Trk family of receptor tyrosine kinases. Fundamental in the vertebrate nervous system, neurotrophin signals have also been suggested as essential for relatively complex nervous systems occurring in invertebrate species that live longer than Caenorhabditis elegans and Drosophila melanogaster. Mammalian neurotrophins have been found to influence invertebrate neuronal growth. However, there are only a few data on the presence of molecules related to neurotrophin signalling components in invertebrates. Our studies provide evidence that analogues of neurotrophins and neurotrophin receptors are expressed in Eisenia foetida earthworms. In particular, NGF-like and Trk-like immunoreactive proteins are both expressed in the nervous system, whereas p75-like positivity identifies tubular structures associated with dorsal pores that are involved in the earthworm response to mechanical irritation or stress.


Bourdieu's field theory applied to the story of the UK radiography profession: A discussion paper.
There are many suggestions offered within the literature to decide if a job type is a profession, some using tick box type trait and characteristics analyses to compare the actions and qualities of individuals to a predefined list. However, there is no specific way to resolve what makes or defines a profession. Writers in many disciplines, including radiography, have used these different models, sometimes with conflicting results. This paper explores the use of Bourdieu's replacement of the concept of profession with that of a 'field', meaning a network of occupants with common attributes, in this case radiographers, in an attempt to resolve this issue. In the UK, radiography practitioners and professional bodies generally use the term profession to describe radiography, and this paper explores a defence of the term for radiography. Using Bourdieu's field theory not only helps define a profession, but also explains the difficulties at the boundaries of professions, and the work needed to protect a profession as a credible entity. This paper supports the argument that radiography is a profession when using Bourdieu's field theory. Radiography continues to work to maintain its status by increasing its symbolic capital by increasing the research output and evidence base of the profession and through role extension. Radiographers can perhaps be assured that radiography is a profession when using Bourdieu's field theory. This paper shows how theoretical frameworks and concepts from outside radiography can be used to support new ways of thinking within the profession.


Thin-film design of amorphous hafnium oxide nanocomposites enabling strong interfacial resistive switching uniformity.
A design concept of phase-separated amorphous nanocomposite thin films is presented that realizes interfacial resistive switching (RS) in hafnium oxide-based devices. The films are formed by incorporating an average of 7% Ba into hafnium oxide during pulsed laser deposition at temperatures ≤400°C. The added Ba prevents the films from crystallizing and leads to ∼20-nm-thin films consisting of an amorphous HfOx host matrix interspersed with ∼2-nm-wide, ∼5-to-10-nm-pitch Ba-rich amorphous nanocolumns penetrating approximately two-thirds through the films. This restricts the RS to an interfacial Schottky-like energy barrier whose magnitude is tuned by ionic migration under an applied electric field. Resulting devices achieve stable cycle-to-cycle, device-to-device, and sample-to-sample reproducibility with a measured switching endurance of ≥104 cycles for a memory window ≥10 at switching voltages of ±2 V. Each device can be set to multiple intermediate resistance states, which enables synaptic spike-timing-dependent plasticity. The presented concept unlocks additional design variables for RS devices.


The impact of laparoscopic technique on the rate of perineal hernia after abdominoperineal resection of the rectum.
To determine the impact of surgical technique on the incidence of perineal hernia after abdominoperineal resection (APR). A retrospective analysis was performed on patients who underwent APR between May 2007 and March 2018 at our institution using our prospectively maintained Colorectal Cancer Database. Demographic and clinical parameters were compared between the open APR (OAPR) and laparoscopic APR (LAPR) groups using Student's t test, chi-squared, or Fisher's exact test. Putative risk factors were then analyzed using a Cox proportional hazard model with perineal hernia as the outcome. The study included 261 patients (191 OAPR and 70 LAPR). Intraoperative blood loss (596.0 ± 633.4 vs. 307.0 ± 307.2 mL, p < 0.001), duration of OR (249.6 ± 115.6 vs. 212.6 ± 75.1 min, p = 0.004), and length of stay (15.6 ± 18.0 vs. 10.4 ± 12.6 days, p = 0.031) were all greater for OAPR than LAPR patients, but wound complications other than hernia did not differ significantly. Perineal hernia was observed in 2.1% of OAPR and 12.9% of LAPR patients. In multivariable analysis, significant risk factors for perineal hernia were age, laparoscopic technique, and closure of the perineal wound with myocutaneous flap (HR 1.08, 11.13, and 31.51, respectively, all p < 0.05). LAPR, although associated with less blood loss and shorter length of hospital stay than OAPR, was a significant risk factor for perineal hernia.


Inhalation bioaccessibility estimation of polycyclic aromatic hydrocarbons from atmospheric particulate matter (PM10): Influence of PM10 composition and health risk assessment.
Polycyclic aromatic hydrocarbons (PAHs) inhalation bioaccessibility was assessed in 65 atmospheric particulate matter samples (PM10) collected at an Atlantic coastal European urban site. The proposed method consists on a physiologically based extraction (PBET) by using Gamble's solution followed by a vortex assisted liquid-liquid micro-extraction (VALLME) and quantification by high performance liquid chromatography with fluorescence detection (HPLC-FLD). The use of a micro-extraction technique combined with FLD detection, provides a simple, fast, sensitive, accurate and low-cost methodology to PAHs quantification in bioaccessible fractions. Accuracy of the bioaccessibility study was assessed by means of a mass balance approaches using a PM10 filter and a certified reference material (ERM-CZ100). High-moderate inhalation bioaccessibilities were found for phenanthrene (Phe), fluoranthene (Ft) and pyrene (Pyr) (average ratios in the 52-65% range); while dibenz (a,h)anthracene (DBahA), indeno (1,2,3-cd)pyrene (IP) and benzo (g,h,i)perylene (BghiP) were observed to be less bioaccessibles (average ratios in the 11-14% range). Relationship between PM10 composition (major ions, trace metals, equivalent black carbon (eBC) and UV-absorbing particulate matter (UVPM)) and PAHs bioaccessibility ratios was also assessed. Principal Component Analysis (PCA) showed that PAHs bioaccessibility percentage is dependent on anthropogenic (eBC, UVPM and Sb concentrations) and marine sources of PM10. Predicted PAHs bioaccessibilities after applying a multiple linear regression model based on marine and anthropogenic source of PM10 could also be established. Health risk assessment of target PM10-associated PAHs via inhalation was assessed considering bioaccessibility concentrations by using hazard index (HI) and BaP equivalent concentration (BaPeq) approaches, suggesting no carcinogenic risk in the area during the sampling campaign.


Repair of sequelae from artificial fiber hair implants with hair-bearing punch grafting.
Several thousand persons had artificial hairs of fiber implanted in their scalps 5 years ago with disastrous results. These persons may still require late repair to remove retained fiber fragments from the skin. The hair-bearing punch graft is a useful method of repair in some patients.


Stimulant and convulsive effects of kynurenines injected into brain ventricles in mice.
Each of six kynurenines tested (DL-kynurenine, quinolinic, 3-hydroxy-anthranilic, xanthurenic, picolinic, and nicotinic acids) injected into brain ventricles in mice in doses of 25--60 mcg produced motor excitement and/or clonic convulsions. Anthranilic acid did not produce these effects. The strongest metabolite was quinolinic acid, which was active in a dose of 1 mcg. It was also the only compound which produced motor excitement and convulsions after intraperitoneal injection (in doses of 400--600 mg/kg, i.e. 10,000--15,000 mcg per mouse). The hypothermic effect of intraventricularly-injected kynurenines was roughly similar to that of intraperitoneally-injected material at 100--1000 times higher doses. These data suggest poor penetration of kynurenines formed in the liver into the brain, and the possible involvement of these metabolites of tryptophan (particularly if they are formed inside the brain) in the mechanism of seizures.


Intrahepatic bile ductal ectasia in autosomal recessive polycystic kidney disease evaluated by fetal magnetic resonance imaging: a more frequent complication.
This study aimed to evaluate liver malformations and intrahepatic bile ductal ectasia and dilatation (IBDED) in cases of prenatal diagnosis of autosomal recessive polycystic kidney disease (ARPKD) using magnetic resonance imaging (MRI). This retrospective study involved 209 cases referred for fetal MRI studies (f-MRI) from March 2004 and December 2019, suspicious of congenital renal disease. Fetuses that met the criteria for ARPKD were selected. Six cases were diagnosed as ARPKD (2.8%). The median gestational age at MRI examination was 28 weeks (24-36 weeks). IBDED was observed in 84% of cases. Moreover, 66% presented multilobar liver lesions, and 33% exhibited monolobar lesions. The "central dot sign" (CDS) was found in half of the cases. In this case series of prenatal diagnosis of ARPKD using f-MRI, IBDED was present in the majority of the cases, and the CDS was noted in half of the cases.


The gut-brain axis in ischemic stroke: its relevance in pathology and as a therapeutic target.
The gut contains the largest reservoir of microorganisms of the human body, termed as the gut microbiota which emerges as a key pathophysiological factor in health and disease. The gut microbiota has been demonstrated to influence various brain functions along the "gut-brain axis". Stroke leads to intestinal dysmotility and leakiness of the intestinal barrier which are associated with change of the gut microbiota composition and its interaction with the human host. Growing evidence over the past decade has demonstrated an important role of these post-stroke changes along the gut-brain axis to contribute to stroke pathology and be potentially druggable targets for future therapies. The impact of the gut microbiota on brain health and repair after stroke might be attributed to the diverse functions of gut bacteria in producing neuroactive compounds, modulating the host's metabolism and immune status. Therefore, a better understanding on the gut-brain axis after stroke and its integration in a broader concept of stroke pathology could open up new avenues for stroke therapy. Here, we discuss current concepts from preclinical models and human studies on the bi-directional communication along the microbiota-gut-brain axis in stroke.


A randomized evaluation of quality-of-life therapy with patients awaiting lung transplantation.
Research shows that patients wait-listed for lung transplantation have very poor quality of life (QOL). This study evaluated the effectiveness of Quality-of-Life Therapy (QOLT) in improving QOL, mood disturbance and social intimacy in adults awaiting lung transplantation. Thirty-five adults were randomized to QOLT (n = 17) or supportive therapy (ST; n = 18) and received individual, telephone-based treatment sessions. QOL, mood and social intimacy assessments were conducted at baseline and at 1 and 3 months after treatment. Repeated measures analyses of variance showed significant Condition x Time interaction effects for all three primary outcome measures. Subsequent post hoc analyses showed that the two groups did not differ significantly at baseline, but did differ significantly at the 1- and 3-month follow-up assessments. When compared to ST patients, QOLT patients had significantly higher QOL scores at the 1- and 3-month assessments, lower mood disturbance scores at the 3-month assessment, and higher social intimacy scores at the 1-month assessment. Results indicate that a patient's QOL, mood state and relationship with the primary caregiver can be positively impacted by a brief psychological intervention prior to lung transplantation.


Investigation of the optimum conditions for electricity generation by haloalkaliphilic archaeon Natrialba sp. GHMN55 using the Plackett-Burman design: single and stacked MFCs.
The production of bioelectricity via the anaerobic oxidation of organic matter by microorganisms is recently receiving much interest and is considered one of the future alternative technologies. In this study, we aimed to produce electrical current by using facultative halophilic archaeon Natrialba sp. GHMN55 as a biocatalyst at the anode of a microbial fuel cell (MFC) to generate electrons from the anaerobic breakdown of organic matter to produce electrical current. Since the MFC's performance can be affected by many factors, the Plackett-Burman experimental design was applied to optimize the interaction between these factors when tested together and to identify the most significant factors that influence bioelectricity generation. We found that the factors that significantly affected electrical current generation were casein, inoculum age, magnet-bounded electrodes, NaCl, resistor value, and inoculum size; however, the existence of a mediator and the pH showed negative effects on bioelectricity production, where the maximum value of the 200 mV voltage was achieved after 48 h. The optimum medium formulation obtained using this design led to a decrease in the time required to produce bioelectricity from 20 days (in the basal medium) to 2 days (in the optimized medium). Also, the overall behavior of the cell could be enhanced by using multiple stacked MFCs with different electrical configurations (such as series or parallel chambers) to obtain higher voltages or power densities than the single chambers where the series chambers were recorded at 27.5 mV after 48 h of incubation compared with 12.6 mV and 1.1 mV for parallel and single chambers, respectively. These results indicate that the order of preferred MFC designs regarding total power densities would be series > parallel > single.


Local treatment of toxoplasmic retinochoroiditis with intravitreal clindamycin and dexamethasone.
To report the clinical outcomes of local treatment of toxoplasmic retinochoroiditis (TRC) with intravitreal injections of clindamycin and dexamethasone. 16 eyes (16 patients) with active TRC sparing the macula and juxtapapillary area treated with intravitreal injections of clindamycin (1 mg) and dexamethasone (1 mg) without concomitant systemic antitoxoplasmic or anti-inflammatory therapy. Measured parameters: Best-corrected visual acuity (BCVA) was measured by an Early Treatment Diabetic Retinopathy Study (ETDRS) chart. BCVA and clinical characteristics of retinochoroiditis were assessed at baseline and at 1, 3, 6, and 12 months. Resolution of retinochoroiditis and changes in BCVA. Control of TRC was achieved in all cases with a mean interval of 2.48 ± 1.03 weeks (2-6 weeks). A single injection of intravitreal clindamycin and dexamethasone was performed in 12 patients, and four patients required two intravitreal injections, during the follow-up period. Fourteen eyes (87.5%) improved ≥ 2 ETDRS lines of BCVA, of two or more Early Treatment Diabetic Retinopathy Study lines, BCVA remained stable in two eyes (12.5%), and no patient had decreased BCVA at the end of the follow-up period. No ocular or systemic adverse events were observed. Local treatment with intravitreal injections of clindamycin and dexamethasone without concomitant systemic therapy was associated with resolution of TRC in patients without macular or juxtapapillary involvement. Intravitreal clindamycin and dexamethasone may represent a viable treatment option in patients with allergies or inadequate responses to oral medications.


Intratumoral immune activation with TLR4 agonist synergizes with effector T cells to eradicate established murine tumors.
Effective T cell-based immunotherapy of solid malignancies requires intratumoral activity of cytotoxic T cells and induction of protective immune memory. A major obstacle to intratumoral trafficking and activation of vaccine-primed or adoptively transferred tumor-specific T cells is the immunosuppressive tumor microenvironment (TME), which currently limits the efficacy of both anti-tumor vaccines and adoptive cell therapy (ACT). Combination treatments to overcome TME-mediated immunosuppression are therefore urgently needed. We combined intratumoral administration of the synthetic toll-like receptor 4 agonist glucopyranosyl lipid A (oil-in-water formulation, G100) with either active vaccination or adoptive transfer of tumor-specific CD8 T cells to mice bearing established melanomas or orthotopically inoculated glioblastomas. In combination with cancer vaccines or ACT, G100 significantly increased expression of innate immune genes, infiltration and expansion of activated effector T cells, antigen spreading, and durable immune responses. Complete tumor regression of both injected and non-injected tumors was observed only in mice receiving combination immunotherapy. TLR4-based intratumoral immune activation may be a viable approach to enhance the efficacy of therapeutic cancer vaccines and ACT in patients.


Importance of temperature and anodic medium composition on microbial fuel cell (MFC) performance.
The performance of a microbial fuel cell (MFC) was investigated at different temperatures and anodic media. A lag phase of 30 h occurred at 30 degrees C which was half that at room temperature (22 degrees C). The maximum power density at 30 degrees C was 70 mW/m(2) and at 22 degrees C was 43 mW/m(2). At 15 degrees C, no successful operation was observed even after several loadings for a long period of operation. Maximum power density of 320 mW/m(2) was obtained with wastewater medium containing phosphate buffer (conductivity: 11.8 mS/cm), which was approx. 4 times higher than the value without phosphate additions (2.89 mS/cm).


The effectiveness of prescription drug monitoring programs at reducing opioid-related harms and consequences: a systematic review.
In order to address the opioid crisis in North America, many regions have adopted preventative strategies, such as prescription drug monitoring programs (PDMPs). PDMPs aim to increase patient safety by certifying that opioids are prescribed in appropriate quantities. We aimed to synthesize the literature on changes in opioid-related harms and consequences, an important measure of PDMP effectiveness. We completed a systematic review. We conducted a narrative synthesis of opioid-related harms and consequences from PDMP implementation. Outcomes were grouped into categories by theme: opioid dependence, opioid-related care outcomes, opioid-related adverse events, and opioid-related legal and crime outcomes. We included a total of 22 studies (49 PDMPs) in our review. Two studies reported on illicit and problematic use but found no significant associations with PDMP status. Eight studies examined the association between PDMP status and opioid-related care outcomes, of which two found that treatment admissions for prescriptions opioids were lower in states with PDMP programs (p < 0.05). Of the thirteen studies that reported on opioid-related adverse events, two found significant (p < 0.001 and p < 0.05) but conflicting results with one finding a decrease in opioid-related overdose deaths after PDMP implementation and the other an increase. Lastly, two studies found no statistically significant association between PDMP status and opioid-related legal and crime outcomes (crime rates, identification of potential dealers, and diversion). Our study found limited evidence to support overall associations between PDMPs and reductions in opioid-related consequences. However, this should not detract from the value of PDMPs' larger role of improving opioid prescribing.