T cells isolated from patients with checkpoint inhibitor-resistant melanoma are functional and can mediate tumor regression.

Background: Almost half of the patients with metastatic melanoma obtain only short-term or no benefit at all from checkpoint inhibitor (CPI) immunotherapy. In this study, we investigated whether the immune system of patients progressing following CPI treatment was able to generate functional tumor-specific immune responses. Materials and methods: Tumor-infiltrating lymphocytes (TILs) were isolated and expanded from metastatic melanoma lesions which progressed during or after anti-programmed cell death protein 1 (PD)-1 and anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) treatment. Tumor-specific immune responses were assessed with co-culture assays of TILs and autologous tumor cells. Results: TILs from 23 metastases of individual patients could be assessed for T cells recognition of autologous tumor cells. All metastases were progressive on or following anti-PD-1 (23/23, 100%), and the majority also after anti-CTLA-4 (17/23, 74%). Functional antitumor immune responses were detected in 19/23 patients (83%). Both CD8+ (in 18/23 patients, 78%) and CD4+ (in 16/23 patients, 70%) TILs were able to recognize autologous tumors. A large fraction of CD8+ TILs (median 23%, range 1.0%-84%) recognized tumor cells. This is similar to the cohorts of unselected patient populations with metastatic melanoma presented in previous studies. The localization of intratumoral immune infiltrates was heterogeneous among samples. In a phase I/II clinical trial, TILs were administered with lymphodepleting chemotherapy, pegIFNα2b and interleukin-2 to 12 patients with CPI-resistant melanoma. Out of 12 patients who previously failed CPI therapy, treatment with TILs resulted in two partial responses, of which one is ongoing. Conclusions: Tumor-reactive T cells appear to heavily infiltrate the tumor microenvironment of patients who failed previous CPI treatment. These patients can still respond to an infusion of unselected autologous TILs. Our results warrant further testing of novel immune re-activation strategies in melanoma patients who failed multiple CPI therapy.

Analysis of a self-propelling sheet with heat transfer through non-isothermal fluid in an inclined human cervical canal.

The present theoretical analysis deals with biomechanics of the self-propulsion of a swimming sheet with heat transfer through non-isothermal fluid filling an inclined human cervical canal. Partial differential equations arising from the mathematical modeling of the proposed model are solved analytically. Flow variables like pressure gradient, propulsive velocity, fluid velocity, time mean flow rate, fluid temperature, and heat-transfer coefficients are analyzed for the pertinent parameters. Striking features of the pumping characteristics are explored. Propulsive velocity of the swimming sheet becomes faster for lower Froude number, higher Reynolds number, and for a vertical channel. Temperature and peak value of the heat-transfer coefficients below the swimming sheet showed an increase by the increment of Brinkmann number, inclination, pressure difference over wavelength, and Reynolds number whereas these quantities decrease with increasing Froude number. Aforesaid parameters have shown opposite effects on the peak value of the heat-transfer coefficients below and above the swimming sheet. Relevance of the current results to the spermatozoa transport with heat transfer through non-isothermal cervical mucus filling an inclined human cervical canal is also explored.

Associations of pain and depression with marital status in patients diagnosed with Parkinson's disease.

BACKGROUND: Depression and pain are significant clinical problems that are comorbid with Parkinson's disease (PD). However, the relationship of these variables with the marital status of patients with PD has not been explored in previous studies. Therefore, the goal of this study was to assess the possible relationship between depression prevalence, depression severity, and pain interference with the marital status of the sufferers of PD. METHODS: This study included 40 patients and 40 healthy control participants who were assessed for depression prevalence and severity using The Hospital Anxiety and Depression Scale (HADS). The same individuals were also assessed for pain interference using the Brief Pain Inventory (BPI). RESULTS: When compared to the control groups, the PD (Single) group was found to have the highest prevalence of depression, followed by the PD (Married) group whereas the Control (Single) group was found to have a higher prevalence than the Control (Married) group (P < 0.0001). A main effect was found on depression severity (P < 0.0001), but no significant differences were observed between the PD groups. Lastly, PD (Single) patients had significantly greater pain interference scores than the PD (Married) patients (P < 0.05) with no other significant case-control or control-control group differences. CONCLUSION: Patient-spouse relationship, which indicates physical and emotional support may have a mitigating effect on patient outcomes of depression prevalence and pain interference.

Screening for Chlamydia trachomatis in Egyptian women with unexplained infertility, comparing real-time PCR techniques to standard serology tests: case control study.

BACKGROUND: To study the prevalence of Chlamydia infection in women with primary and secondary unexplained infertility using ELISA technique for antibody detection and real time, fully automated PCR for antigen detection and to explore its association with circulating antisperm antibodies (ASA). METHODS: A total of 50 women with unexplained infertility enrolled in this case control study and a control group of 44 infertile women with a known cause of infertility. Endocervical specimens were collected for Chlamydia antigen detection using PCR and serum samples for antibodies detection. Circulating anti-sperm antibodies were detected using sperm antibody Latex Agglutination tests. RESULTS: The overall prevalence of Chlamydial infection in unexplained infertility cases as detected by both ELISA and PCR was 40 % (20/50). The prevalence of current Chlamydial genital infection as detected by real-time PCR was only 6.0 % (3/50); two of which were also IgM positive. Prevalence of ASA was 6.0 % (3/50); all were sero-negative for anti-C.trachomatis IgM and were PCR negative. CONCLUSION: The incidence of Chlamydial infection in Egyptian patients with unexplained infertility is relatively high. In the setting of fertility investigations; screening for anti. C.trachomatis antibodies using ELISA, and treatment of positive cases should be considered. The presence of circulating ASA does not correlate with the presence of old or current Chlamydia infection in women with unexplained infertility.

A mathematical model for the flow of a Casson fluid due to metachronal beating of cilia in a tube.

A mathematical model is developed to study the transport mechanism of a Casson fluid flow inspired by the metachronal coordination between the beating cilia in a cylindrical tube. A two-dimensional system of nonlinear equations governing the flow problem is formulated by using axisymmetric cylindrical coordinates and then simplified by employing the long wavelength and low Reynolds number assumptions. Exact solutions are derived for the velocity components, the axial pressure gradient, and the stream function. However, the expressions for the pressure rise and the volume flow rate are evaluated numerically. The features of the flow characteristics such as pumping and trapping are illustrated and discussed with the help of graphs. It is observed that the volume flow rate is influenced significantly by the width of plug flow region H p as well as the cilia length parameter ε. The analysis is also applied and compared with the estimated value of the volume flow rate of epididymal fluid in the ductus efferentes of the human male reproductive tract.

Influence of the narrow {111} planes on axial and planar ion channeling.

We report channeling patterns where clearly resolved effects of the narrow {111} planes are observed in axial and planar alignments for 2 MeV protons passing through a 55 nm [001] silicon membrane. At certain axes, such as <213> and <314>, the offset in atomic rows forming the narrow {111} planes results in shielding from the large potential at the wide {111} planes, producing a region of shallow, asymmetric potential from which axial channeling patterns have no plane of symmetry. At small tilts from such axes, different behavior is observed from the wide and narrow {111} planes. At planar alignment, distinctive channeling effects due to the narrow planes are observed. As a consequence of the shallow potential well at the narrow planes, incident protons suffer dechanneled trajectories which are excluded from channeling within the wide planes, resulting in an anomalously large scattered beam at {111} alignment.

Flow analysis of Carreau fluid model induced by the ciliary cells, smooth muscle cells and pressure gradient at the ampullar region entrance.

This theoretical analysis considers a biomechanical model in which the Carreau fluid model characterizes the viscoelastic nature of growing human embryo and secreted fluid. This model incorporates transport mechanisms that involve the swaying motions of ciliary cells, peristaltic contractions of smooth muscle cells and pressure gradient at the ampullar region entrance. Series form solutions of the resulting partial differential equations are obtained using the regular perturbation method. A theoretical estimate of effects of the condition of pressure gradient, geometric parameters and fluid model parameters on the flow variables that have relevance to the problem of growing embryo transport in the human fallopian tube is presented through the discussion of graphs. Furthermore, an analogy between the linearly viscous fluid, and the shear thinning and shear thickening characteristics of the Carreau fluid model is also presented. The pertinence of the obtained results with growing embryo transport in the human fallopian tube revealed that when shear thickening characteristics of the Carreau fluid model are considered then complete mitotic divisions take place properly with an estimated appropriate residue time about 3-4 days. Smaller size trapped boluses of the secreted fluid make the smooth forwarding of the growing embryo in the human fallopian tube when shear thinning characteristics of the Carreau fluid model are taken into account. Key modulators: progesterone ([Formula: see text] and estradiol ([Formula: see text]), prostaglandin [Formula: see text] ([Formula: see text]) and prostaglandin [Formula: see text] ([Formula: see text]) constraint the growing embryo transport.

Mathematical assessment of the spermatozoa transport through couple stress fluid in an asymmetric human cervical canal.

Swimming of spermatozoa through couple stress fluid in an asymmetric human cervical canal is investigated in the present theoretical analysis. A couple of fourth-order partial differential equations arising from the mathematical modelling of the proposed model is solved analytically. Flow variables like pressure gradient, propulsive velocity, mucus velocity and time mean flow rate are analysed for the pertinent parameters. Conspicuous features of the pumping characteristics are explored. It is found that pressure rise facilitates the motion of spermatozoa to fertilize an ovum in the female reproductive tract, whereas pressure drop by inverting the direction of spermatozoa controls the probability of pregnancy. Maximal propulsive velocity of the spermatozoa is reported in the absence of travelling waves along the cervical walls. Minute impact of phase difference on propulsive velocity is evident. An analogy of the current analysis with the existing literature is also made.

Analysis of the peristaltic-ciliary flow of Johnson-Segalman fluid induced by peristalsis-cilia of the human fallopian tube.

The present prospective theoretical analysis concerns with the peristalsis-cilia induced transport of a developing embryo from ampulla to intramural, in the human fallopian tube. A model of peristalsis-cilia induced flow of the Johnson-Segalman fluid within fallopian tubal fluid in a finite two dimensional narrow tube is developed. We solved highly non-linear PDE emerging from the modeling of proposed model using perturbation method. The series expressions for flow variables like axial and radial velocities, pressure gradient, stream function, volume flow rate and time mean volume flow rate are derived. The numerical integration is performed for appropriate residue time over tube length and pressure difference over wavelength. The analysis delineated that, involved parameters and constants have vice versa effects on axial velocity and appropriate residue time over tube length. Striking features of the pumping characteristics and the trapping phenomenon are discussed in detail. Furthermore, comparison of the peristaltic flow with the peristaltic-ciliary flow and Johnson-Segalman fluid with the linearly viscous fluid is made. It is revealed that appropriate residue time of the Johnson-Segalman fluid in the narrow tube is 3-4 days, which agreed with the time taken by the developing embryo from ampulla to intramural, in the human fallopian tube.

Rapid screening for group B Streptococcus in near-term pregnant women by Granada™ biphasic broth.

BACKGROUND: Prenatal screening for group B Streptococcus (GBS) colonization can reduce the incidence of neonatal GBS infections. We aimed to improve the screening-based approach of GBS in a limited resources antenatal care clinic by using Strep B Granada™ Biphasic Broth. METHODS: This study included 80 pregnant women between 35 and 37 weeks of gestation, who attended the antenatal care clinic of Kasr El-Aini University Hospital from November 2013 to January 2014. Two high vaginal swabs were collected, then transported using Amies transport medium. One vaginal swab was processed by conventional culture-based methods on 5% sheep blood agar plates. The other swab was immersed in 3 mL selective enrichment broth (Granada™ Biphasic Broth bioMérieux). RESULTS: Among 80 pregnant women, GBS was detected in 9 (11.25%) of the studied cases within 18-24 hours. Detection of orange-red colonies in GBS Granada broth was 100% specific for the presence of beta-hemolytic group B streptococci. CONCLUSION: Using Granada biphasic broth media was easy, affordable and shortened the turnaround time needed for the detection of GBS by conventional culture methods. Routine screening of pregnant women for vaginal GBS colonization by Granada™ Biphasic broth would allow properly timed prenatal antimicrobial prophylaxis to prevent possible neonatal infections.

Prevalence of human papilloma virus (HPV) and its genotypes in cervical specimens of Egyptian women by linear array HPV genotyping test.

BACKGROUND: The association of human papillomavirus (HPV) with cervical cancer is well established. AIM: To investigate HPV genotype distribution and co-infection occurrence in cervical specimens from a group of Egyptian women. METHODS: A group of 152 women with and without cervical lesions were studied. All women had cervical cytology and HPV testing. They were classified according to cytology into those with normal cytology, with squamous intraepithelial lesions (SIL) and invasive squamous cell carcinoma (SCC). Cervical samples were analyzed to identify the presence of HPV by PCR, and all positive HPV-DNA samples underwent viral genotype analysis by means of LINEAR ARRAY HPV Genotyping assay. RESULTS: A total of 26 HPV types with a prevalence of 40.8 % were detected. This prevalence was distributed as follows: 17.7 % among cytologically normal females, 56.5, 3.2, and 22.6 % among those with LSIL, HSIL and invasive SCC respectively. Low-risk HPV types were detected in 81.8 % of the cytologically-normal women, in 5.7 % of those in LSIL women, and in 14.3 % of infections with invasive SCC, while no low-risk types were detected in HSIL. High-risk HPV types were detected in 18.2 % of infections in the cytologically normal women, 14.3 % of infections in LSIL, and in 21.4 % of invasive lesions. The probable and possible carcinogenic HPV were not detected as single infections. Mixed infection was present in 80 % of women with LSIL, in 100 % of those with HSIL, and in 64.3 % of those with invasive SCC. This difference was statistically significant. HPV 16, 18 and 31 were the most prevalent HR HPV types, constituting 41.9, 29.03 and 12.9 % respectively, and HPV 6, 62 and CP6108 were the most prevalent LR HPV types constituting 11.3, 9.7 and 9.7 % respectively. CONCLUSION: These data expand the knowledge concerning HPV prevalence and type distribution in Egypt which may help to create a national HPV prevention program. HPV testing using the LINEAR ARRAY HPV Genotyping assay is a useful tool when combined with cytology in the diagnosis of mixed and non-conventional HPV viral types.

Oral antioxidants supplementation for women with unexplained infertility undergoing ICSI/IVF: randomized controlled trial.

OBJECTIVE: Good oocyte quality and maturity are important prerequisites for high fertilization and implantation rates in IVF/ICSI treatment cycles. Reactive oxygen species (ROS) are produced within ovarian follicles, especially during the ovulation process, and increased ROS activity may be a cause of impaired oocyte maturation and higher rate of failure of IVF/ICSI cycles. STUDY DESIGN: RCT evaluating the effect of antioxidant supplementation on ICSI/IVF outcomes. Two hundred and eighteen women with unexplained subfertility undergoing IVF/ICSI were randomized into two groups. The study group (n = 112) received daily oral antioxidants in the form of multivitamins and minerals (amino acid chelated) while the control group (n = 106) did not. Main outcomes were number of mature metaphase II (MII) oocytes and clinical pregnancy rate. RESULTS: There were no significant changes between the groups as regards age, BMI, basal FSH, number of mature (MII) oocytes (12.7 ± 9.4 vs. 13.2 ± 8.6, P = 0.7) and clinical pregnancy rate per woman randomized (38% vs. 34%; [OR = 1.2; 95% CI, 0.70-2.11]. CONCLUSION: Oral antioxidants in the form of a combination of multivitamins and minerals (amino acid chelated) did not improve oocyte quality and pregnancy rates in women with unexplained infertility undergoing IVF/ICSI treatment.

The effect of air mass origin on the ambient concentrations of 7Be and ²¹°Pb in Islamabad, Pakistan.

Concentration of radionuclides ²¹°Pb and 7Be, having half lives of 22.3 years and 53.29 days, respectively, in the surface air samples of Islamabad (33.38°N, 73.10°E and Altitude ∼536 m asl.) are measured. The non-destructive technique of gamma-spectrometry, with a high purity germanium HPGe detector, was employed for the analysis of all samples. The annual average concentrations of ²¹°Pb and 7Be in the surface air samples were determined as 0.284 ± 0.15 and 3.171 ± 1.14 mBq m⁻³, respectively. Our results have shown a seasonal variation of the concentration of 7Be in air samples with high values for the spring season. High concentrations for ²¹°Pb are obtained when air masses originate from plain areas of Pothohar region, located in the South-West, West and North West of Islamabad. Our values of concentrations show a nice agreement with the relevant reported results.

A quantitative cytochemical study of determination for xylem-element formation in response to wounding in roots of Pisum sativum L.

Quantitative cytochemical studies of cortical parenchyma cells of roots of Pisum sativum in which the central vascular bundle is severed, showed esterase activity to be an early marker of the determination of cells to form a vascular bridge. Explantation, onto a basal culture medium, of wound segments taken from roots at different times after severing the stele showed the irreversibility of the esterase activity on removal from the inducing environment, so confirming this as a marker of cell determination. A general determination for the stele was shown to occur by 8-10 h after wounding, but information relating to tracheid secondary-cell-wall formation was not apparently available until 18-20 h after wounding. Determination appeared to occur well before mitosis. The timings of the differentiation steps indicate a simple diffusion model to explain the mechanism of arrival of the initiating molecules.

Activation of carboxylesterases in root cortical parenchymal cells of Pisum sativum during xylem induction in vitro.

A quantitative cytochemical study of naphthol AS-D esterase activity in explants from roots of Pisum sativum grown on basal medium for 3 or 6 days showed similar levels of activity to those seen in sections of cortex and stele from intact roots of similar ages. Explants grown in the presence of auxins or cytokinin alone showed a threefold or twofold increase in cortical parenchymal activity, respectively. On adding both hormones to initiate xylem element formation, there was also a threefold increase in activity in the cortex. In all three cases, the stimulated activity was totally inhibited by either 10(-4) M diisopropylfluorophosphate (DFP) or 10(-4) M diethyl p-nitrophenylphosphate (E600), indicating carboxylesterase activity. The low level of activity normally present in cortical cells was inhibitor resistant, so indicating acetylesterase activity. Thus, auxins and cytokinins appear to activate mainly similar carboxylesterases during the initiation of xylem elements from cortical parenchyma cells.

A quantitative cytochemical method for phosphofructokinase in plant tissues.

A quantitative cytochemical method for the demonstration of phosphofructokinase has been successfully applied to a range of plant tissues. The findings indicate that this enzyme system may be assayed as an indicator of glycolytic activity in plant cells, and furthermore tha the very high endogenous phosphoenolpyruvate concentrations may not be rate limiting in vivo.

Enhanced planar channeling of MeV protons through thin crystals.

At certain tilt alignments between a MeV proton beam and a planar channeling direction, a single interface lattice rotation within a crystal can result in a lower rate of dechanneling than at planar alignment in a perfect crystal. Such planar channeling enhancement arises when the beam passes through a layer thickness which is a half-multiple of the oscillation wavelength and then encounters a small interface rotation which is matched to the beam tilt angle. The beam is projected into the center of the phase space ellipse below the interface, resulting in certain trajectories undergoing a reduction in their transverse energy, in a manner analogous to stochastic cooling or atom laser cooling.

Observation of many coherent oscillations for MeV protons transmitted through stacking faults.

High spatial resolution, high-contrast transmission channeling images of stacking faults in silicon have been produced using a beam of 2 MeV protons focused to a spot size of 60 nm. Over a narrow range of beam tilts to the (011) planes, up to ten periodic intensity oscillations are observed, providing evidence of a long-range coherency of the planar channeled trajectories. This behavior is characterized using Monte Carlo computer simulations, and a phase-space model of planar channeled ion interactions with stacking faults is developed which incorporates all observed channeling and blocking phenomena.