Examining the association between pruritus and quality of life in patients with atopic dermatitis treated with crisaborole.

BACKGROUND: Pruritus is a leading cause of reduced health-related quality of life (QoL) in atopic dermatitis (AD). Crisaborole ointment is a non-steroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate AD. In identical Phase 3 studies (NCT02118766, NCT02118792), crisaborole reduced disease and pruritus severity versus vehicle. OBJECTIVE: Quantify the relationship between pruritus and QoL using data from these studies. METHODS: Patients aged ≥2 years were randomly assigned 2 : 1 to receive crisaborole:vehicle twice daily for 28 days. QoL was measured at baseline and day 29 using the Dermatology Life Quality Index (DLQI; patients aged ≥16 years), the Children's Dermatology Life Quality Index (CDLQI; patients aged 2-15 years) and the Dermatitis Family Impact (DFI; caregivers of patients aged 2-17 years). Pruritus was measured using the Severity of Pruritus Scale (SPS), a 4-point scale from 0 ('no itching') to 3 ('bothersome itching/scratching that disturbs sleep'), and captured morning and evening via electronic diary. Data from crisaborole and vehicle arms were pooled for this analysis. A repeated-measures longitudinal model was used to estimate relationships between pruritus (SPS) and QoL (DLQI, CDLQI and DFI in separate analyses). RESULTS: One thousand five hundred and twenty two patients received crisaborole or vehicle. A linearity assumption for the relationship between SPS and DLQI (n = 294), CDLQI (n = 1200), and DFI (n = 1293) was appropriate. For DLQI, SPS score of 0 was associated with 'no negative effect on patient QoL'; SPS score of 1 was associated with 'small effect on patient QoL'; SPS score of 2 was associated with 'moderate effect on patient QoL'; and SPS score of 3 was associated with 'very large effect on patient QoL'. The pattern of relationships between SPS and CDLQI and DFI was similar. CONCLUSIONS: The relationships between SPS and DLQI, CDLQI and DFI substantiate the significant link between pruritus and patient/caregiver QoL in AD.

Lyman-α source for laser cooling antihydrogen.

We present a Lyman-α laser developed for cooling trapped antihydrogen. The system is based on a pulsed Ti:sapphire laser operating at 729 nm that is frequency doubled using an LBO crystal and then frequency tripled in a Kr/Ar gas cell. After frequency conversion, this system produces up to 5.7 µW of average power at the Lyman-α wavelength. This laser is part of the ATRAP experiment at the antiproton decelerator in CERN.

Case of disseminated histoplasmosis in a HIV-infected patient revealed by nasal involvement with maxillary osteolysis.

BACKGROUND: Disseminated Histoplasmosis (DH) is a rare manifestation of Acquired Immune Deficiency Syndrome (AIDS) in European countries. Naso-maxillar osteolysis due to Histoplasma capsulatum var. capsulatum (Hcc) is unusual in endemic countries and has never been reported in European countries. Differential diagnoses such as malignant tumors, cocaine use, granulomatosis, vasculitis and infections are more frequently observed and could delay and/or bias the final diagnosis. CASE PRESENTATION: We report the case of an immunocompromised patient infected by Human Immunodeficiency Virus (HIV) with naso-maxillar histoplasmosis in a non-endemic country. Our aim is to describe the clinical presentation, the diagnostic and therapeutic issues. A 53-year-old woman, originated from Haiti, was admitted in 2016 for nasal deformation with alteration of general condition evolving for at least 6 months. HIV infection was diagnosed in 2006 and classified at AIDS stage in 2008 due to cytomegalovirus infection associated with pulmonary histoplasmosis. At admission, CD4 cell count was 9/mm3. Surgical biopsies were performed and ruled out differential or associated diagnoses. Mycological cultures identified Hcc and Blood Polymerase Chain Reaction (PCR) for Hcc was positive. The patient was given daily Amphothericin B liposomal infusion during 1 month. Hcc PCR became negative in the blood under treatment, and then oral switch by itraconazole was introduced. Antiretroviral treatment was reintroduced after a 3-week histoplasmosis treatment. Normalization of naso-maxillar mucosa enabled a palatal prosthesis. CONCLUSION: Naso-maxillar histoplasmosis is extremely rare; this is the first case ever reported in a non-endemic country. Differential diagnoses must be ruled out by conducting microbiologic tools and histological examinations on surgical biopsies. Early antifungal treatment should be initiated in order to prevent DH severe outcomes.

Is Chemotherapy or Radiation Therapy in Addition to Surgery Beneficial for Locally Advanced Rectal Cancer in the Elderly? A National Cancer Data Base (NCDB) Study.

INTRODUCTION: Current National Comprehensive Cancer Network guidelines for Stages II and III rectal cancer recommend neoadjuvant chemoradiation followed by curative intent surgery and adjuvant chemotherapy. It is unclear whether therapies in addition to surgery are truly beneficial in elderly patients. Our aim was to compare the survival of patients over 80 with Stages II and III rectal cancer undergoing curative intent surgery with or without additional therapy. MATERIALS AND METHODS: The National Cancer Data Base (NCDB 2006-2011) was queried for patients over 80 with Stages II and III rectal cancer. The primary outcome was overall survival. Patients were stratified based upon therapy group. Univariate group comparisons were made. Unadjusted Kaplan-Meier and multivariable Cox proportional hazards modeling survival analyses were performed. RESULTS: The query yielded 3098 patients over 80 with Stage II (N = 1566) or Stage III (N = 1532) disease. Approximately, half of the patients received surgery only. Kaplan-Meier analysis showed improved survival for patients receiving neoadjuvant and/or adjuvant therapy in addition to surgery, but there was no significant difference between those that received guideline concordant care (GCC), neoadjuvant chemoradiation only, or post-operative chemotherapy only. Cox proportional hazard modeling identified age >90 and margin positivity as independent risk factors for decreased overall survival. CONCLUSION: Analysis of NCDB data for Stages II and III rectal cancer in patients over 80 shows a survival benefit of adjuvant and/or neoadjuvant therapy over surgery alone. There does not appear to be a difference in survival between patients who received neoadjuvant chemoradiation, post-resection adjuvant chemotherapy, or GCC.

Improvement of biohydrogen production using a reduced pressure fermentation.

This study investigated the effect of reduced pressure on biohydrogen production in an upflow anaerobic sludge blanket (UASB) reactor from whey permeate. The results showed that the reduced pressure fermentation was more effective in enhancing biohydrogen production than dark fermentative hydrogen production at atmospheric pressure. Mesophilic fermentative biohydrogen production was investigated at a constant hydraulic retention time (HRT) of 24 h and increasing organic loading rates (OLRs) of 20, 25, 30, 35 kg COD/m(3) day. The reduced pressure fermentation was successfully operated at all OLRs tested. The maximum proportion of hydrogen in biogas of 47.7 %, volumetric hydrogen production rate (VHPR) of 7.10 L H2/day and hydrogen yield of 4.55 mol H2/kg COD removed occurred at the highest OLR. Increase in OLR affected the hydrogen production in UASB reactor exploited at atmospheric pressure. The reduced pressure process was able to remarkably improve the biohydrogen performance at high OLRs.

Determination of the η(')-proton scattering length in free space.

Taking advantage of both the high mass resolution of the COSY-11 detector and the high energy resolution of the low-emittance proton beam of the cooler synchrotron COSY, we determine the excitation function for the pp→ppη(') reaction close to threshold. Combining these data with previous results, we extract the scattering length for the η(')-proton potential in free space to be Re(a(pη(')))=0±0.43 fm and Im(a(pη(')))=0.37(-0.16)(+0.40) fm.

Effectiveness of dairy wastewater treatment in a bioreactor based on the integrated technology of activated sludge and hydrophyte system.

The aim of this study was to determine the effectiveness of dairy wastewater treatment in the integrated technology based on the simultaneous use of the activated sludge method (AS) and a hydrophyte system (HS) (AS-HS), in this case, common reed (Phragmites australis) or common cattail (Typha latifolia). Experiments were conducted in an innovative reactor exploited in the fractional-technical scale at the loads of 0.05 mg BOD5/mg.d.m. d (biochemical oxygen demand) and 0.10 mg BOD5/mg.d.m d. The AS--HS enabled improving the removal effectiveness ofbiogenes characterized by concentrations of Ntot., N-NH4 and Ptot. In contrast, the integrated system had no significant reducing effect either on concentrations of organic compounds characterized by BOD5 and chemical oxygen demand parameters or on the structure of AS in the sequencing batch-type reactors.

Respirometric studies on the effectiveness of biogas production from wastewaters originating from dairy, sugar and tanning industry.

The objective of the present study was to determine the effectiveness of biogas production during methane fermentation of wastewaters originating from the dairy, tanning and sugar industries, by means ofrespirometric measurements conducted at a temperature of 35 degrees C. Experiments were carried out with the use of model tanks of volume 0.5 dm3. A high production yield of biogas, with methane content exceeding 60%, was achieved in the case of the anaerobic treatment of wastewaters from the dairy and sugar industries. A significantly lower effect was observed in the case of tanning wastewaters. The effectiveness of the fermentation process decreased with increasing loading of the tanks with a feedstock of organic compounds. By loading a model tank with this feedstock, the effectiveness of treatment ranged from 62.8% to 71.4% residual chemical oxygen demand for dairy wastewaters and from 57.9% to 64.1% for sugar industry wastewaters. The efficiency of organic compound removal from tanning wastewaters was below 50%, regardless of the method applied.

Adipokines in interstitial lung diseases.

Interstitial lung diseases (ILD) are a heterogenic group of respiratory diseases with complex pathogenesis. A growing number of evidence suggests role of adipose tissue and it's hormones (adipokines) in pathogenesis of various disorders, including lung tissue diseases. The aim of this study was to assess the concentrations of selected adipokines and their receptors (apelin, adiponectin, chemerin, chemerin receptor - CMKLR1) in patients with IPF (idiopathic pulmonary fibrosis) and sarcoidosis in comparison to healthy controls. We found changes in adipokines concentrations in ILD. Adiponectin concentrations were higher in all respiratory diseases patients in comparison to healthy controls. Apelin concentration in ILD patients was higher then those in healthy subjects. The trend of chemerin and CMKLR1 concentrations were similar, with highest concentrations seen in sarcoidosis. The study shows a difference of adipokines concentrations between patients with ILD and healthy controls. Adipokines are a potential marker and therapeutic target in patients with IPF and sarcoidosis.

Use of transcranial low-intensity focused ultrasound for targeted delivery of stem cell-derived exosomes to the brain.

The blood-brain barrier (BBB) presents a significant challenge for targeted drug delivery. A proposed method to improve drug delivery across the BBB is focused ultrasound (fUS), which delivers ultrasound waves to a targeted location in the brain and is hypothesized to open the BBB. Furthermore, stem cell-derived exosomes have been suggested as a possible anti-inflammatory molecule that may have neural benefits, if able to pass the BBB. In the present study, transcranial low-intensity focused ultrasound (LIFU), without the use of intravenous microbubbles, was assessed for both (1) its ability to influence the BBB, as well as (2) its ability to increase the localization of intravenously administered small molecules to a specific region in the brain. In vivo rat studies were conducted with a rodent-customized 2 MHz LIFU probe (peak pressure = 1.5 MPa), and injection of labeled stem cell-derived exosomes. The results suggested that LIFU (without microbubbles) did not appear to open the BBB after exposure times of 20, 40, or 60 min; instead, there appeared to be an increase in transcytosis of the dextran tracer. Furthermore, the imaging results of the exosome study showed an increase in exosome localization in the right hippocampus following 60 min of targeted LIFU.

Second-harmonic generation from coupled plasmon modes in a single dimer of gold nanospheres.

We show that a dimer made of two gold nanospheres exhibits a remarkable efficiency for second-harmonic generation under femtosecond optical excitation. The detectable nonlinear emission for the given particle size and excitation wavelength arises when the two nanoparticles are as close as possible to contact, as in situ controlled and measured using the tip of an atomic force microscope. The excitation wavelength dependence of the second-harmonic signal supports a coupled plasmon resonance origin with radiation from the dimer gap. This nanometer-size light source might be used for high-resolution near-field optical microscopy.

Trapped antihydrogen in its ground state.

Antihydrogen atoms (H¯) are confined in an Ioffe trap for 15-1000 s-long enough to ensure that they reach their ground state. Though reproducibility challenges remain in making large numbers of cold antiprotons (p¯) and positrons (e(+)) interact, 5±1 simultaneously confined ground-state atoms are produced and observed on average, substantially more than previously reported. Increases in the number of simultaneously trapped H¯ are critical if laser cooling of trapped H¯ is to be demonstrated and spectroscopic studies at interesting levels of precision are to be carried out.

Adiabatic cooling of antiprotons.

Adiabatic cooling is shown to be a simple and effective method to cool many charged particles in a trap to very low temperatures. Up to 3×10(6) p are cooled to 3.5 K-10(3) times more cold p and a 3 times lower p temperature than previously reported. A second cooling method cools p plasmas via the synchrotron radiation of embedded e(-) (with many fewer e(-) than p in preparation for adiabatic cooling. No p are lost during either process-a significant advantage for rare particles.

Effect of mechanical strain on the optical properties of quantum dots: controlling exciton shape, orientation, and phase with a mechanical strain.

We show how a nanomechanical strain can be used to dynamically reengineer the optics of quantum dots, giving a tool to manipulate mechanoexciton shape, orientation, fine structure splitting, and optical transitions, transfer carriers between dots, and interact qubits for quantum processing. Most importantly, a nanomechanical strain reengineers both the magnitude and phase of the exciton exchange coupling to tune exchange splittings, change the phase of spin mixing, and rotate the polarization of mechanoexcitons, providing phase and energy control of excitons.

Centrifugal separation of antiprotons and electrons.

Centrifugal separation of antiprotons and electrons is observed, the first such demonstration with particles that cannot be laser cooled or optically imaged. The spatial separation takes place during the electron cooling of trapped antiprotons, the only method available to produce cryogenic antiprotons for precision tests of fundamental symmetries and for cold antihydrogen studies. The centrifugal separation suggests a new approach for isolating low energy antiprotons and for producing a controlled mixture of antiprotons and electrons.

Determination of the total width of the η' meson.

Taking advantage of both the low-emittance proton beam of the cooler synchrotron COSY and the high momentum precision of the COSY-11 detector system, the mass distribution of the η' meson was measured with a resolution of 0.33 MeV/c2 (FWHM), improving the experimental mass resolution by almost an order of magnitude with respect to previous results. Based on the sample of more than 2300 reconstructed pp → ppη' events, the total width of the η' meson was determined to be Γ(η') = 0.226 ± 0.017(stat) ± 0.014(syst) MeV/c2.

What do we (not) know about how paracetamol (acetaminophen) works?

WHAT IS KNOWN AND BACKGROUND: Although paracetamol (acetaminophen), N-(4-Hydroxyphenyl)acetamide, is one of the world's most widely used analgesics, the mechanism by which it produces its analgesic effect is largely unknown. This lack is relevant because: (i) optimal pain treatment matches the analgesic mechanism to the (patho)physiology of the pain and (ii) modern drug discovery relies on an appropriate screening assay. OBJECTIVE: To review the clinical profile and preclinical studies of paracetamol as means of gaining insight into its mechanism of analgesic action. METHODS: A literature search was conducted of clinical and preclinical literature and the information obtained was organized and reviewed from the perspective of its contribution to an understanding of the mechanism of analgesic action of paracetamol. RESULTS: Paracetamol's broad spectrum of analgesic and other pharmacological actions is presented, along with its multiple postulated mechanism(s) of action. No one mechanism has been definitively shown to account for its analgesic activity. WHAT IS NEW AND CONCLUSION: Further research is needed to uncover the mechanism of analgesic action of paracetamol. The lack of this knowledge affects optimal clinical use and impedes drug discovery efforts.

Is there a therapeutic effect of botulinum toxin on scalp alopecia? Physiopathology and reported cases: A systematic review of the literature.

Botulinum toxin is a treatment whose effectiveness has been widely demonstrated in the treatment of facial wrinkles. Its use in alopecia has been much less studied in the literature. Therefore, we carried out a systematic review of the literature in December 2019 in order to index published cases of alopecia patients treated with botulinum toxin. Pub Med, Embase, and Cochrane Library databases were explored. Six studies that included 94 patients were selected. Only one study was prospectively controlled against placebo. Of the 94 patients, 85 were affected by androgenetic alopecia, 8 by alopecia areata, and 1 by radiation-induced alopecia. The doses injected per session varied between 30 and 150 units and the number of sessions between 1 and 12. In the majority of the studies, the injections were carried out in all the muscles of the scalp (frontal, temporal, peri-auricular, occipital). Four studies showed a frank improvement in hair growth. Two of them showed improvement in hair density using an objective endpoint (hair count). The remaining reported studies showed inconclusive results. Patient satisfaction was high across all studies, but this systematic review did not clearly demonstrate the value of using the botulinum toxin in the treatment of alopecia. Subsequent prospective randomized controlled studies are required.

CD4+CD25highCD127low/-FoxP3 + Regulatory T-Cell Population in Acute Leukemias: A Review of the Literature.

Regulatory T-cells (Tregs) are a very important subtype of lymphocytes when it comes to self-control in the human immunological system. Tregs are decisive not only in the protection against destruction of own tissues by autoimmune immunocompetent cells but also in the immunological answer to developing cancers. On the other hand, Tregs could be responsible for the progression of acute and chronic leukemias. In our study, we review publications available in the PUMED database concerning acute leukemia, with a particular emphasis on child's leukemias. The percentage of regulatory T-lymphocytes in peripheral blood and bone marrow was elevated compared to those in healthy individuals and correlated with progressive disease. Regulatory T-cells taken from children diagnosed with leukemia showed a higher suppressive capability, which was confirmed by detecting elevated levels of secreted IL-10 and TGF-beta. The possibility of pharmacological intervention in the self-control of the immunological system is now under extensive investigation in many human cancers. Presumably, Treg cells could be a vital part of targeted therapies. Routine Treg determination could be used to assess the severity of disease and prognosis in children with acute lymphoblastic leukemia. This proposition results from the fact that in some studies, higher percentage of Treg cells in peripheral blood was demonstrated. However, observations confirming these facts are scarce; thus, extrapolating them to the population of children with hematological malignancies needs to be verified in additional studies.

An ecohydrological approach to the river contamination by PCDDs, PCDFs and dl-PCBs - concentrations, distribution and removal using phytoremediation techniques.

The levels of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and dioxin-like polychlorinated biphenyls (dl-PCBs) in the Pilica River and Sulejów Reservoir were found to be 46% higher during the flood season than during stable flow periods. In addition, PCDD/PCDF and dl-PCB mass loads increased by 5- to 12-fold and by 23- to 60-fold for toxic equivalency (TEQ) during flooding. The Sulejów Reservoir was found to play a positive role in reducing PCDD, PCDF and dl-PCB transport within the study period, with reductions ranging from 17 to 83% for total concentrations, and 33 to 79% for TEQ. Wastewater Treatment Plants (WTPs) were not efficient at mass concentration removal, with small displaying the least efficiency. WTPs discharge pollutants into the aquatic environment, they also produce sludge that requires disposal, similar to reservoir sediments. Sludge- or sediment-born PCDDs, PCDFs and dl-PCBs may be removed using phytoremediation. The cultivation of cucumber and zucchini, two efficient phytoremediators of organic pollutants, on polluted substrate resulted in a mean decrease in PCDD + PCDF + dl-PCB TEQ concentrations: 64% for cucumber and 69% for zucchini in sludge-amended soil, and by 52% for cucumber and 51% for zucchini in sediment-amended soil.