Imbalance of Follicular Helper and Follicular Regulatory T Cells in Chronic Rhinosinusitis with Nasal Polyps.

OBJECTIVE: Data regarding the imbalance in follicular helper T (Tfh) and follicular regulatory T (Tfr) cell responses in patients having chronic rhinosinusitis with nasal polyps (CRSwNP) is so far limited. Thus, we aimed to assess the changes in circulating Tfh and Tfr in CRSwNP patients. METHODS: This case-control study included 21 patients having CRSwNP and 20 age and sex-matched healthy blood donors as a control group. Lund-Mackay staging system was used for radiologic scoring of chronic rhinosinusitis. Two milliliters of peripheral blood samples were collected from all participants into EDTA-containing vacutainer tubes to assess the levels of Tfh and Tfr cells using flow cytometry. RESULTS: Patients having CRSwNP did not show significant differences in the percentages of CD4+ T cells and total CD4+CXCR5+ T cells from healthy controls. Meanwhile, levels of both activated circulating Tfh and Tfr showed a marked rise in patients than controls. In addition, a positive correlation was observed between the levels of both activated Tfh and Tfr cells. CONCLUSION: An imbalance in circulating Tfh/Tfr levels was detected in patients having CRSwNP. A significant rise in the levels of Tfh and Tfr was detected in patients proposing a possible role of this imbalance in disease pathogenesis.

Perception of the interaction behavior between pepsin and the antimicrobial drug secnidazole with combined experimental spectroscopy and computer-aided techniques.

Drug-pepsin interaction possibly affects pepsin activity, leads to undesirable shift of its functionality, and likely induces adverse effects in the gastrointestinal tract. The present study aims at exploring the interaction of pepsin with the antiprotozoal/antibacterial drug secnidazole adopting a combination of experimental spectroscopy and computational techniques. For this purpose, different spectroscopic methods including fluorescence, synchronous fluorescence, UV-Visible absorption, and infrared spectroscopy were adopted and coordinated with in silico analysis via molecular docking. The employed synchronized approaches evidenced that; pepsin interacted with secnidazole via static mechanism at stomach pH inferring some consequent conformational changes in the structure of pepsin. Thermodynamic study of drug-pepsin interaction demonstrated that the interaction is spontaneous via van der Waals and hydrogen bonding interaction and the orientation of ligand within pepsin cavity was illustrated by molecular docking. The synchronous fluorescence study proved that tyrosine amino acid residues were involved in the interaction more than tryptophan amino acid residues. Eventually, the combined experimental and molecular docking approaches suggest that secnidazole interacts with pepsin and alter its structure, that finding correlates to gastrointestinal side effects related to secnidazole oral administration.

Delineation of T cell subsets in chronic rhinosinusitis with nasal polyps.

Objectives: Detailed characterisation of CD45RA+ and CD45RO+ T cell subsets in both CD4+ and CD8+ cells in blood and tissue of patients with chronic rhinosinusitis with nasal polyps (CRSwNP) is lacking. We aimed to investigate T cell differentiation levels in blood and tissue and correlate this with CT score and white blood cell count. Methods: This case-control study was conducted on 21 patients with CRSwNP and 20 healthy controls. Lund-Mackay score was used for radiologic staging of chronic rhinosinusitis. T cell subsets were characterised in blood and nasal polyp tissue using CD4, CD8, CCR7, CD45RA, CD45RO, CD27, and CD95 monoclonal antibodies. Results: Most variations in T cell subsets were detected in tissue rather than blood. A higher level of CD8+ TCM, CD4+ TSCMs and lower level of CD8+ TEM were detected in the blood of CRSwNP patients vs controls. In CRSwNP patients, substantial decrease of tissue CD8+ TNs, CD8+ TCMs, CD4+ TNs, and CD4+TSCMs with marked increase in the percentages of TEMs and TEMRAs were detected among CD4+ and CD8+ T cells compared with levels in blood. Conclusions: The reduction of TNs, TSCMs, and TCMs and accumulation of TEMs and TEMRAs subsets that function as effector cells in sinonasal mucosa, especially CD8+ T cells, might indicate the role of immunomodulation of memory/effector T-cells in the pathogenesis of CRSwNP.

Effect of lidocaine infusion on intraoperative bleeding during functional endoscopic sinus surgery: a randomized controlled trial.

BACKGROUND: It is crucial to reduce bleeding during functional endoscopic sinus surgery (FESS). Our primary goal was to evaluate the effect of intravenous lidocaine infusion (ILI) as an adjunct to the enhanced recovery after surgery (ERAS) protocols on intraoperative bleeding during FESS. We hypothesized that ILI could improve the surgical field. METHODS: Forty-three adult patients ASA I-II, 20-50 years old, undergoing FESS under general anesthesia were randomly assigned to receive immediately after induction of anesthesia either ILI 1.5 mg/kg as a bolus followed by 1.5 mg/kg/ h until the end of surgery (Group L) or normal saline (Group NL). Intraoperative blood loss, bleeding and surgeon satisfaction scores, mean arterial pressure (MAP), heart rate (HR), extubation and eye-opening times, and time to first analgesic request were recorded. RESULTS: Intraoperative bleeding and bleeding scores in the first 45 min after ILI were decreased, with better surgeon satisfaction in Group L (P<0.05). MAP and HR values were lower after ILI in Group L during surgery (P<0.05). Extubation and eye-opening times were shorter (P=0.001) and the time to first analgesic request was prolonged (P=0.001) in Group L than in Group NL. CONCLUSIONS: ILI decreased intraoperative blood loss and improved the surgical field visibility in the first 45 min during FESS.

Delorme's operation plus sphincteroplasty for complete rectal prolapse associated with traumatic fecal incontinence.

Rectal prolapse associated with traumatic fecal incontinence is a rare clinical combination. This study was designed to assess Delorme's operation with sphincteroplasty as a surgical management of this combination in terms of recurrence and improvement of fecal incontinence. In this prospective study, we enrolled patients suffering from short, full-thickness rectal prolapse associated with traumatic fecal incontinence who had been admitted to Alexandria Main University Hospital during the period of May 2010-January 2013. Preoperative data including cause of trauma, duration of symptoms, results of anal manometry, and degree of fecal incontinence using Wexner score were collected from all patients. Delorme's procedure with overlap sphincteroplasty was done in all patients. Recurrence of prolapse and improvement of fecal incontinence were assessed after 1, 3, 6 and 12 months. The study included 13 patients aged (32±8.7) years, 9 females and 4 males. Cause of sphincteric injury included previous anal surgery in 7 patients and normal labor in 6 patients. Duration between sphincteric injury and operation was (8.08±2.47) months. Preoperative Wexner's mean score was 16.07±3.4. Early postoperative complications included superficial wound infection (69.2%), minor wound dehiscence (61.5%), and postoperative bleeding (7.6%). Recurrence was detected in 1 patient at 6 month follow-up. Wexner's score showed significant improvement for all patients after 6 months (4.00±2.04). In conclusion, combination of Delorme's procedure and sphincteroplasty for treatment of patients with short complete rectal prolapse associated with traumatic fecal incontinence is a safe, effective surgical management with satisfactory results regarding anatomical and functional outcomes.

Experimental demonstration of non-iterative interpolation-based partial ICI compensation in100G RGI-DP-CO-OFDM transport systems.

We experimentally investigate the performance of a low-complexity non-iterative phase noise induced inter-carrier interference (ICI) compensation algorithm in reduced-guard-interval dual-polarization coherent-optical orthogonal-frequency-division-multiplexing (RGI-DP-CO-OFDM) transport systems. This interpolation-based ICI compensator estimates the time-domain phase noise samples by a linear interpolation between the CPE estimates of the consecutive OFDM symbols. We experimentally study the performance of this scheme for a 28 Gbaud QPSK RGI-DP-CO-OFDM employing a low cost distributed feedback (DFB) laser. Experimental results using a DFB laser with the linewidth of 2.6 MHz demonstrate 24% and 13% improvement in transmission reach with respect to the conventional equalizer (CE) in presence of weak and strong dispersion-enhanced-phase-noise (DEPN), respectively. A brief analysis of the computational complexity of this scheme in terms of the number of required complex multiplications is provided. This practical approach does not suffer from error propagation while enjoying low computational complexity.

Enrichment materials do not negatively affect reproductive success and offspring survival and weight in mice.

Environmental enrichment is designed to improve the overall welfare of laboratory animals, including mice. Few studies have directly assessed the effects of different types of enrichment on mouse offspring survival and growth. The authors examined how survival and growth of C57BL/6 mouse pups are affected by three kinds of cage enrichment materials: compressed cotton squares, two-ply tissues and plastic igloos. During the last week of gestation and the first two weeks postpartum, the authors observed cages with litters and noted use of the enrichment materials, quality of nest construction, number of pups per litter and weight of pups. Both the first and second litters were evaluated for each dam. Dams and pups had continuous contact with the enrichment materials, especially cotton squares and tissues. Neither the presence nor the type of enrichment material influenced the survival and weight of offspring, suggesting that the use of such materials does not negatively impact reproductive success or offspring survival.

Cyclosporine-A as a neuroprotective agent against stroke: its translation from laboratory research to clinical application.

Stoke remains a leading cause of death and disability with limited treatment options. Extensive research has been aimed at studying cell death events that accompany stroke and how to use these same cell death pathways as potential therapeutic targets for treating the disease. The mitochondrial permeability transition pore (MPTP) has been implicated as a major factor associated with stroke-induced neuronal cell death. MPTP activation and increased permeability has been shown to contribute to the events that lead to cell death. Cyclosporine A (CsA), a widely used immunosuppressant in transplantation and rheumatic medicine, has been recently shown to possess neuroprotective properties through its ability to block the MPTP, which in turn inhibits neuronal damage. This newfound CsA-mediated neuroprotection pathway prompted research on its use to prevent cell death in stroke and other neurological conditions. Preclinical studies are being conducted in hopes of establishing the safety and efficacy guidelines for CsA use in human trials as a potential neuroprotective agent against stroke. In this review, we provide an overview of the current laboratory and clinical status of CsA neuroprotection.

The significance of Epstein Barr virus (EBV) & DNA topoisomerase II alpha (DNA-Topo II alpha) immunoreactivity in normal oral mucosa, oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC).

BACKGROUND: Head and neck cancer including oral cancer is considered to develop by accumulated genetic alterations and the major pathway is cancerization from lesions such as intraepithelial dysplasia in oral leukoplakia and erythroplakia. The relationship of proliferation markers with the grading of dysplasia is uncertain. The involvement of EBV in oral carcinogenesis is not fully understood. AIM: The present study was designed to investigate the role of EBV and DNA Topoisomerase II proportional (DNA-Topo II proportional) during oral carcinogenesis and to examine the prognostic significance of these protein expressions in OSCCs. METHODS: Using specific antibodies for EBV and DNA-Topo II proportional, we examined protein expressions in archival lesion tissues from 16 patients with oral epithelial dysplasia, 22 oral squamous cell carcinoma and 20 normal oral mucosa by immunohistochemistry. Clinical information was obtained through the computerized retrospective database from the tumor registry. RESULTS: DNA-Topo II proportional was expressed in all examined specimens. Analysis of Variance ANOVA revealed highly significant difference (P < 0.01) in young aged labial tissues and significant (P < or = 0.05) in gingival and not significant (P > 0.05) in inferior surface of tongue and in hard palatal tissues. Significant differences were observed between OEDs and NSE (P < 0.001) and SCCs and controls (P < 0.001), also, significant differences could be observed between SCCs and OEDs. DNA-Topo II proportional expression was significantly higher in tumors of low differentiation versus tumors of moderate and high differentiation (P < 0.001), DNA-Topo II proportional expression was correlated with age, tumor size, tumor stage, node metastasis and tumor differentiation, but not with gender and tumor site. None of normal squamous epithelium (NSE) expressed EBV. Heterogeneous reactivity for EBV was observed through the series of dysplasia and squamous cell carcinoma. Its expression increased progressively with lymph node metastasis and low tumor differentiation, but no significant association could be observed with other clinicopathological parameters. EBV protein expression was increased with elevated Topo II-proportional LI in OEDs and OSCCs. A tendency to positive correlation between EBV and Topo II proportional, variant expression was observed in OEDs but not in OSCCs. CONCLUSION: EBV and DNA Topo II-alphaLI expression are possible indicators in oral carcinogenesis and may be valuable diagnostic and prognostic indices in oral carcinoma.