Cyclin-dependent kinase 5 (CDK5) inhibitors in Parkinson disease.

Cyclin-dependent kinase 5 (Cdk5) is a protein expressed in postmitotic neurons in the central nervous system (CNS). Cdk5 is activated by p35 and p39 which are neuron regulatory subunits. Cdk5/p35 complex is activated by calpain protease to form Cdk5/p35 which has a neuroprotective effect by regulating the synaptic plasticity and memory functions. However, exaggerated Cdk5 is implicated in different types of neurodegenerative diseases including Parkinson disease (PD). Therefore, modulation of Cdk5 signalling may mitigate PD neuropathology. Therefore, the aim of the present review was to discuss the critical role of Cdk5 in the pathogenesis of PD, and how Cdk5 inhibitors are effectual in the management of PD. In conclusion, overactivated Cdk5 is involved the development of neurodegeneration, and Cdk5/calpain inhibitors such as statins, metformin, fenofibrates and rosiglitazone can attenuate the progression of PD neuropathology.

Design of an IMI optical 2 × 4 decoder circuit based on square disk resonators.

This paper presents the design of a 2×4 decoder that was developed by using the finite element method (FEM) in conjunction with the COMSOL version 5.5 software. Insulator-metal-insulator (IMI) waveguides with four substructures were used in the fabrication of the plasmonic decoder. Gold is used as a conducting material. This is a challenge for us, while Teflon is used as a dielectric material in the fabrication process. The dimensions of this part are 1090 nm by 400 nm. At an operating wavelength of 1550 nm, the transmission threshold (T t h r e s h o l d ) of this scheme has been determined to be 10%. In order to assess the effectiveness of the plasmonic decoder, it is recommended that the modulation depth (MD), contrast ratio (CR), and insertion loss (IL) parameters be carried out. Both the highest values of CR and MD are 12.33 decibels, and the maximum value of MD is 99.96%. It is because of these qualities that this work is distinguished from earlier works.

The link between metabolic syndrome and Alzheimer disease: A mutual relationship and long rigorous investigation.

It has been illustrated that metabolic syndrome (MetS) is associated with Alzheimer disease (AD) neuropathology. Components of MetS including central obesity, hypertension, insulin resistance (IR), and dyslipidemia adversely affect the pathogenesis of AD by different mechanisms including activation of renin-angiotensin system (RAS), inflammatory signaling pathways, neuroinflammation, brain IR, mitochondrial dysfunction, and oxidative stress. MetS exacerbates AD neuropathology, and targeting of molecular pathways in MetS by pharmacological approach could a novel therapeutic strategy in the management of AD in high risk group. However, the underlying mechanisms of these pathways in AD neuropathology are not completely clarified. Therefore, this review aims to elucidate the association between MetS and AD regarding the oxidative and inflammatory mechanistic pathways.

The conceivable role of prolactin hormone in Parkinson disease: The same goal but with different ways.

Parkinson disease (PD) is a progressive neurodegenerative disease (NDD) of the brain. It has been reported that prolactin (PRL) hormone plays a differential effect in PD, may be increasing, reduced or unaffected. PRL level is dysregulated in different neurodegenerative disorders including PD. Preclinical and clinical studies pointed out that PRL may has a neuroprotective against PD neuropathology . Though, the mechanistic role of PRL in PD is not fully elucidated. Therefore, the objective of the present review was to clarify the potential role and mechanistic pathway of PRL in PD neuropathology. The present review highlighted that PRL appears to have a neuroprotective effect against PD neuropathology by inhibiting the expression of pro-inflammatory signaling pathways, antioxidant effects and by inhibiting neuroinflammation. Thus, preclinical and clinical studies are warranted in this regard.

5 × 5 Gbps DWDM optical system with DCF and cascaded repeaters techniques.

Dispersion and attenuation problems are the most important factors that limit dense wavelength division multiplexing (DWDM) system performance. Dispersion causes pulse broadening of the optical spectrum, and the attenuation degrades the optical signal. In this paper, dispersion compensation fiber (DCF) and cascaded repeaters techniques have been proposed to reduce linear and nonlinear problems by using two different modulation formats (carrier-suppressed return zero [CSRZ] and optical modulator) and two various channel spacings (100 and 50 GHz). The cascaded repeater offers the best performance at 100 GHz channel spacing with 37 quality factors for CSRZ and optical modulation schemes; however, the DCF network design is more compatible with the CSRZ modulation format with 27 quality factors. For 50 GHz channel spacing, the cascaded repeater offers the best performance with 31 quality factors for CSRZ and optical modulator techniques; the DCF technique comes in next with 27 quality factors for CSRZ and 19 for optical modulators.

Design of DWDM optical communication systems with different modulation formats using DCF and a repeater.

The dense wavelength division multiplexing (DWDM) technique has been used to provide a large capacity and low bandwidth loss for optical communication systems. In this paper, simulation designs by Optisystem15.0 of carrier-suppressed return to zero (CSRZ), differential phase shift keying (DPSK), and intensity modulation is proposed to determine which modulation format is more compatible with four and eight DWDM channels for transmitting an optical signal over 400 km distance. For a long optical path, the dispersion compensation fiber (DCF) technique is proposed to eliminate dispersion effects and increase the possibility of transmitting multiple optical wavelengths over long single-mode fiber. Optical amplifiers are used to amplify the optical signal with a distorted signal and process the attenuation caused by the long transmission distance. In DCF network design, CSRZ offers the best performance because of the large quality factor (24.560) and high threshold power (15 dBm), which make the system compatible with increased distance between the transmitter and receiver; next is intensity modulation with a 24.5604 quality factor and 13 dBm threshold power value; DPSK comes in last with the worst performance, with a quality factor of 10 at 13 dBm power due to non-linear effects, especially non-linear phase noise. In the repeater design, the DPSK modulation format has the best performance with a large quality factor of 20.7913 at a high threshold power of 14 dBm for 150 GHz spacing; this is because the repeater technique is compatible with reducing the non-linear effects of the DPSK format. CSRZ and intensity modulation have the same performance with a 12 quality factor at 4 dBm power for intensity modulation and 3 dBm power for CSRZ modulation.

Orchiepididymitis in the context of multisystem inflammatory syndrome in a child with Covid-19 from Syria: a very rare presentation for SARS-Cov-19 in children.

The coronavirus disease 2019 (COVID-19) is still striking the global population affecting all age groups. So far, many clinical features associated with COVID-19 illness remain under-identified, especially atypical manifestations. It is essential to characterize associated rare symptoms to better recognize complications. As severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes Multisystem Inflammatory Syndrome in children (MIS-C) in severe infection manifesting as a generalized inflammatory reaction and immune response in many body systems, potential involvement of the male urogenital tract by SARS-CoV-2 should be considered. Herein, we report a case of a pediatric patient with orchiepididymitis associated with COVID-19 infection, emphasizing the importance of considering other manifestations such as genital involvement of MIS-C in children with COVID-19 and highlighting the need to monitor the genitourinary function after infection. Therefore, andrological consultation is necessary to evaluate fertility as a long-term follow-up, especially as the effects of SARS-CoV-2 on male reproductive function are still to be thoroughly researched.

Acute Kidney Injury During Hospitalization Increases the Risk of VTE.

BACKGROUND: Kidney disease has been linked to risk for hospitalization-related (HR) VTE, but the effect size and differences across types of kidney disease are described poorly. RESEARCH QUESTION: Can the risk for HR VTE among patients with acute kidney injury (AKI) and chronic kidney disease be quantified, and if so, how? STUDY DESIGN AND METHODS: We prospectively collected data on hospitalized adult patients and documented HR VTE events. We recorded creatinine clearance (CrCl) daily throughout hospitalization and modeled the effects that admission CrCl, peak CrCl, average CrCl, and AKI had on HR VTE. We controlled for known VTE risk factors and daily administration of chemoprophylaxis. RESULTS: Of the 6,552 admissions that met our inclusion criteria, 184 (2.81%) patients experienced an HR VTE. Surgery, AKI, chemical prophylaxis, and admission albumin all were associated with HR VTE in univariate analysis, but neither admission CrCl nor average CrCl (throughout the hospitalization) increased the odds of HR VTE. Kaplan-Meier curves showed AKI, whether it occurred before or during the hospitalization, was associated significantly with time to HR VTE. Cox regression analysis found that AKI was associated independently with HR VTE, as was surgery during admission, enoxaparin dose, and admission albumin. Sensitivity analyses showed that AKI lost significance when only patients with traumatic injuries were assessed. INTERPRETATION: We found that AKI increases the risk for HR VTE in a large, heterogeneous population that included medical and surgical patients. However, this relationship was not seen in patients with traumatic injuries.

Effect of Nasal Skin Type on Skin Problems following Rhinoplasty.

Skin problems following rhinoplasty may cause dissatisfaction concerning the esthetic expectations of the patients. This study was conducted to determine whether nasal skin type has an effect on skin problems after rhinoplasty. Thirty-five patients undergoing rhinoplasty in our tertiary referral center between May 2018 and August 2019 were included in the study. The nasal skin sebum level was measured with Sebumeter preoperatively and patients were divided into two groups according to the median sebum level. Among the 35 patients, half of them with higher nasal skin sebum were categorized as oily skin group (n = 17; 14 males, 3 females; mean sebum level: 200.3 ± 26.9), and the other half were categorized as dry skin group (n = 18; 10 males, 8 females; mean sebum level: 101.9 ± 38). Periorbital edema and ecchymosis were assessed at postoperative days 1, 3, and 7. Acne and seborrhea severity determined with Global Acne Grading System and Seborrheic Dermatitis Area Severity Index the day before operation and postoperative days 7 and 14 and months 1, 3, and 10. Compared with dry skin group, upper eyelid ecchymosis score at postoperative day 7 was statistically higher in oily skin group (p = 0.044). There was no significant difference in upper eyelid edema scores between postoperative days 1 and 3 for oily skin group (p = 0.020). No statistically significant differences were found for acne and seborrhea severity. Nasal skin sebum levels may affect periorbital edema and ecchymosis after the procedure but no significant effect has been observed for acne and seborrhea. Predicting the effect of nasal skin types on these problems may help the surgeon to inform patients more correctly.

Comparison of anesthetic agents on otoacoustic emissions in children: propofol vs ketamine.

BACKGROUND: Otoacoustic emission (OAE) tests are important evaluation tools for diagnosis of peripheral auditory pathology. Sedation or general anesthesia may be required for the performance of the OAE tests. The aim of this retrospective study was to compare the effects of anesthetic agents, propofol and ketamine, on OAEs in children. METHODS: Fifty healthy children who underwent tonsillectomy and/or adenoidectomy under general anesthesia were included in this study. Three anesthesia induction protocols were defined for this study and the anesthesiologist applied his or her own choice. Transient evoked otoacoustic emissions (TEOAEs) and distortion-product otoacoustic emissions (DPOAEs) were automatically recorded in both ears of each patient prior to anesthetic (predrug) and following the loss of consciousness 5 min later (postdrug) by an audiologist blinded to the method of anesthesia. Acceptable TEOAEs were defined as signal noise ratio (S/N) of above 3 dB SPL (decibel sound pressure level) and DPOAEs of 6 dB SPL or above. Between-group and within-group comparisons and correlations were performed for statistical analysis. RESULTS: Retrospective review of the anesthesia charts from 44 cases that completed the study showed that propofol, ketamine, and sevoflurane induction protocols were used in 21, 18, and 5 cases, respectively. Measurements of 36 ears in the propofol group and 34 ears in the ketamine group were included in the final analysis. Postdrug TEOAE and DPOAE amplitudes were significantly lower than predrug amplitudes except at 8 kHz in the ketamine group. There was no significant statistical difference in postdrug DPOAE measurements between propofol and ketamine groups but a significant difference was observed at 2 and 3 kHz of postdrug TEOAE measurements. TEOAE measurements were below 3 dB in 8 of 34 ears after ketamine and in 1 of 36 ears after propofol administration. There was a significant difference between the groups with respect to the incidence of successful measurements of TEOAEs. The DPOAE measurements were affected less by these drugs. CONCLUSION: DPOAE measurements were reduced similarly by propofol and ketamine anesthesia. Lower false outcome ratio in TEOAE measurements made propofol a better option than ketamine.

The human nail--barrier characterisation and permeation enhancement.

The human nail remains one of the most challenging membranes for formulation scientists to target and for clinicians to heal. Its formidable barrier properties are the primary reason that oral therapy remains the primary approach to manage ungual infections. This article considers the major structural properties underlying the excellent barrier function of the nail, with particular emphasis on the role of biophysical methods in advancing our knowledge of this appendage. Formulations currently available for management of ungual disease are discussed and their therapeutic efficacy is assessed. Finally, experimental strategies to enhance ungual permeation are reviewed and prospects for future developments in the field are considered.

Cyclin D1 amplification in tongue and cheek squamous cell carcinoma.

INTRODUCTION: Several molecular markers have been studied for their usefulness as prognostic markers in oral squamous cell carcinoma (OSCC). One such molecular marker is cyclin D1 which is a proto-oncogene located on 11q13 in humans. OBJECTIVE: To explore the feasibility of using cyclin D1 as a prognostic marker in tongue and cheek SCC by the fluorescent-in-situ hybridization (FISH) method. METHODS: Fifty paraffin-embedded samples (25 each of cheek and tongue SCCs) were obtained from the archives of the Oral Pathology Diagnostic Laboratory. Sociodemographic data, histopathologic diagnoses, lymph node status and survival data were obtained from the Malaysian Oral Cancer Database and Tissue Bank System (MOCDTBS)coordinated by the Oral Cancer Research and Coordinating Centre (OCRCC), University of Malaya. The FISH technique was used to detect the amplification of cyclin D1 using the Vysis protocol. Statistical correlations of cyclin D1 with site and lymph node status were analyzed using the Fisher exact test. Kaplan-Meier and Log Rank (Mantel-Cox) test were used to analyze cyclin D1 amplification and median survival time. RESULTS: Positive amplification of cyclin D1 was detected in 72% (36) of OSCCs. Detection of positive amplification for cyclin D1 was observed in 88% (22) and 56% (14) of the tongue and cheek tumors, respectively, where the difference was statistically significant (P=0.012). Lymph node metastasis of cheek SCCs showed a trend towards a significant association (P= 0.098) with cyclin D1 amplification whereas the lymph node metastasis of tongue SCC was clearly not significant (P=0.593).There was a statistically significant correlation between cyclin D1 positivity and survival rate (P=0.009) for overall SCC cases and (P<0.001) for cheek SCC cases. CONCLUSION: The present study found that cyclin D1 amplification may differ in different subsites of OSCC (tongue vs cheek) and its positive amplification implies an overall poor survival in OSCCs, particularly those arising in cheeks.

Treatment with rituximab, dexamethasone, high-dose cytarabine, and oxaliplatin (R-DHAOx) produces a strong long-term antitumor effect in previously treated patients with follicular non-Hodgkin's lymphoma.

BACKGROUND: We explored the addition of rituximab to high-dose cytarabine (ara-C), oxaliplatin (L-OHP), and dexamethasone [R-DHAOx], in resistant and relapsed patients with CD20-positive follicular non-Hodgkin's lymphoma. METHODS: Twenty-two patients were included; they were treated previously with one to five chemotherapy regimens, including 13 patients who had also received rituximab. R-DHAOx consisted of rituximab, 375mg/m(2), day 1; dexamethasone, 40mg/d, days one to four; L-OHP, 130mg/m(2), day 1; and ara-C, 2000mg/m(2) every 12 h, day 2. Courses were repeated every 21 days for eight courses. RESULTS: Twenty-one patients (95%) achieved a complete response and one had a partial response. Responses were obtained in patients with and without resistance to prior treatment, either alone or combined with rituximab. The median follow-up time was 58.3 months (range, 8.7-92.6 months). Progression-free survival reached a plateau at 84% at 38.2 months. Only two of the 21 complete responders have relapsed. Tumor molecular markers disappeared in all 10 complete responders whose markers were found before treatment. Peripheral neuropathy related to the cumulative dose of L-OHP, and myelosuppression were the most prominent toxic effects. CONCLUSIONS: R-DHAOx is highly active for salvage treatment of patients with follicular non-Hodgkin's lymphoma, and it produces long-term antitumor efficacy.