Candida albicans blastospores and hyphae respond differentially to fluconazole: additional virulence factor of germination process

Background: The morphologic transition from yeasts (blastospores) to hyphae, through the germination process, is a crucial virulence factor of Candida albicans ( C. albicans), as it enhances adherence, tissue invasion and biofilm formation. The study aimed at comparing fluconazole susceptibility patterns of C. albicans yeast and germinated forms. Methods: Six C. albicans strains, including C. albicans ATCC 10231 and 5 clinical isolates were tested in yeast forms and germinated forms for fluconazole susceptibility using CLSI M27-A3 broth microdilution and CLSI M44-A2 disk diffusion reference methods. Results: Fluconazole minimal inhibitory concentrations (MICs) were 0.125-1 µg/ml and 0.25-4 µg/ml for yeasts and germinated forms, respectively. The sensitivities of yeasts were higher than those of their corresponding germinated forms with 1 to 4-fold dilutions differences. The MIC50s of yeasts and germinated forms were 0.125 and 1 µg/ml, respectively, with 3-fold dilution difference, while MIC90s were 1 and 4 µg/ml for yeasts and germinated forms, respectively, with 2-fold dilution difference. Means of inhibition zones were 31-46.7 mm and 29.3-43.7 mm for yeasts and germinated forms, respectively. The germinated forms of all tested strains had inhibition zones smaller than those of their corresponding yeast forms with 0.2-4.8 mm differences. There was significant statistical difference in sizes of inhibition zones between yeasts and germinated forms (p = 0.043). Conclusions: Yeast and hyphae of C. albicans, both in planktonic state, respond differentially to fluconazole, as the hyphae are less sensitive than their yeasts counterparts, which can be considered as a virulence factor for hyphae, which should be considered in treatment plans of candidal infections.&nbsp

Impact of plant density of pea intercropped with flax under different nitrogen fertilizer levels on crop productivity

A field experiment was established to analyze the effect of different plant densities of pea (12.5, 25.0, 37.5 and 50.0% of the recommended plant density "RPD") intercropped with 100% flax under nitrogen fertilization levels (60, 85 and 110 kg N/ha) on yield of both crops, their competitive relationships and economic evaluation. A Split-plot design with three replications was used, where the main-plots were assigned to nitrogen fertilization levels and the sub-plots for intercropping patterns. Application of 85 kg N/ha significantly increased all studied characters of both crops. Sowing flax with pea with 12.5%  from the RPD resulted in highest values of flax stem diameter, straw yield/ha, number of capsules/plant, seeds/plant, seed index and seed yield/ha. For pea higher values were also observed for number of leaves, branches and pods/plants, pod length and diameter, green pod weight and number of seeds/pod. The highest values of total green pods yield/ha of pea was produced when flax is sown with the RPD and pea with 37.5% RPD. It can be concluded that the maximum LER, RCC, total income and economic return were obtained from sowing flax with the RPD and pea with 37.5% RPD and fertilizing with 85 kg N/ha. Keywords: Flax, pea, intercropping system, plant densities, nitrogen fertilizer levels, competitive relationship

Effect of aerobic exercise, slow deep breathing and mindfulness meditation on cortisol and glucose levels in women with type 2 diabetes mellitus: a randomized controlled trial.

Background: Aerobic exercise combined with breathing exercise can be an integral part of diabetes mellitus treatment. This single-center, randomized, parallel-group study investigated the effect of the combination of aerobic exercise with slow deep breathing and mindfulness meditation on the glucose and cortisol levels of women with type 2 diabetes mellitus (T2DM). Materials and Methods: Fifty-eight middle-aged women with T2DM (mean age: 45.67 ± 2.92 years) were randomly assigned to either the aerobic training group (AT: n = 29; mean age [46.1 ± 2.7 years]) or the aerobic exercise combined with slow deep breathing and mindfulness meditation (AT + DMM: n = 29; mean age [45.24 ± 3.14 years]). Aerobic exercise was performed at 60%-75% of the maximum heart rate. The women in each group were asked to perform the training three times weekly over a 6-week period. The duration of each session was 40 min for the AT group and 60 min for the AT + DMM group. The two groups were asked to perform aerobic exercise at 60%-75% of the maximum heart rate. Their fasting blood glucose (FBG) and serum cortisol levels were measured at the baseline and after the 6 weeks. Results: Compared with the AT group, the group undertaking 6 weeks of aerobic training combined with slow, deep breathing exercises and mindfulness meditation showed significantly lower levels of FBG (p = 0.001) and cortisol levels (p = 0.01) than the AT group. Conclusion: The addition of slow deep breathing and mindfulness meditation to aerobic exercise can better control the glucose and cortisol levels of women with T2DM and thereby improve their outcomes and decrease their cardiometabolic risk

Effect of aerobic exercise, slow deep breathing and mindfulness meditation on cortisol and glucose levels in women with type 2 diabetes mellitus: a randomized controlled trial

Background: Aerobic exercise combined with breathing exercise can be an integral part of diabetes mellitus treatment. This single-center, randomized, parallel-group study investigated the effect of the combination of aerobic exercise with slow deep breathing and mindfulness meditation on the glucose and cortisol levels of women with type 2 diabetes mellitus (T2DM). Materials and Methods: Fifty-eight middle-aged women with T2DM (mean age: 45.67 ± 2.92 years) were randomly assigned to either the aerobic training group (AT: n = 29; mean age [46.1 ± 2.7 years]) or the aerobic exercise combined with slow deep breathing and mindfulness meditation (AT + DMM: n = 29; mean age [45.24 ± 3.14 years]). Aerobic exercise was performed at 60%–75% of the maximum heart rate. The women in each group were asked to perform the training three times weekly over a 6-week period. The duration of each session was 40 min for the AT group and 60 min for the AT + DMM group. The two groups were asked to perform aerobic exercise at 60%–75% of the maximum heart rate. Their fasting blood glucose (FBG) and serum cortisol levels were measured at the baseline and after the 6 weeks. Results: Compared with the AT group, the group undertaking 6 weeks of aerobic training combined with slow, deep breathing exercises and mindfulness meditation showed significantly lower levels of FBG (p = 0.001) and cortisol levels (p = 0.01) than the AT group. Conclusion: The addition of slow deep breathing and mindfulness meditation to aerobic exercise can better control the glucose and cortisol levels of women with T2DM and thereby improve their outcomes and decrease their cardiometabolic risk

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Mortality of emergency abdominal surgery in high-, middle- and low-income countries

Background: Surgical mortality data are collected routinely in high-income countries, yet virtually no low- or middle-income countries have outcome surveillance in place. The aim was prospectively to collect worldwide mortality data following emergency abdominal surgery, comparing findings across countries with a low, middle or high Human Development Index (HDI). Methods: This was a prospective, multicentre, cohort study. Self-selected hospitals performing emergency surgery submitted prespecified data for consecutive patients from at least one 2-week interval during July to December 2014. Postoperative mortality was analysed by hierarchical multivariable logistic regression. Results: Data were obtained for 10 745 patients from 357 centres in 58 countries; 6538 were from high-, 2889 from middle- and 1318 from low-HDI settings. The overall mortality rate was 1⋅6 per cent at 24 h (high 1⋅1 per cent, middle 1⋅9 per cent, low 3⋅4 per cent; P < 0⋅001), increasing to 5⋅4 per cent by 30 days (high 4⋅5 per cent, middle 6⋅0 per cent, low 8⋅6 per cent; P < 0⋅001). Of the 578 patients who died, 404 (69⋅9 per cent) did so between 24 h and 30 days following surgery (high 74⋅2 per cent, middle 68⋅8 per cent, low 60⋅5 per cent). After adjustment, 30-day mortality remained higher in middle-income (odds ratio (OR) 2⋅78, 95 per cent c.i. 1⋅84 to 4⋅20) and low-income (OR 2⋅97, 1⋅84 to 4⋅81) countries. Surgical safety checklist use was less frequent in low- and middle-income countries, but when used was associated with reduced mortality at 30 days. Conclusion: Mortality is three times higher in low- compared with high-HDI countries even when adjusted for prognostic factors. Patient safety factors may have an important role. Registration number: NCT02179112 (http://www.clinicaltrials.gov)

Rotary Traveling-Wave Oscillators for Millimeter-Wave Radars

This thesis focuses on the design, analysis, and implementation of a low phase noise (PN) rotary traveling-wave oscillator (RTWO) system that meets the stringent PN requirements of millimeter-wave (mmW) radar in the 76-81 GHz band. There are three main objectives of this work. The first is to explore techniques for reducing the flicker noise upconversion in an RTWO. The second is to find new techniques to enhance the DC-to-RF efficiency and to lower the power consumption of a frequency quadrupler by exploiting the multi-phase nature of an RTWO. Third, the feasibility of implementing an RTWO with an embedded phase-to-digital converter (PDC) at 10 GHz will be investigated. The thesis begins by discussing the stringent PN requirements in a frequency-modulated continuous-wave (FMCW) radar system in the 76-81 GHz band. Then, the PN requirements of an RTWO-based all-digital phase-locked loop (ADPLL), and considerably the RTWO, are derived for different frequency bands; 10, 20, and 26 GHz. Then, the novel "distributed stubs" technique is introduced to mitigate the flicker noise upconversion mechanism in mmW RTWOs. A comprehensive mathematical analysis is demonstrated to analyze the flicker noise upconversion mechanism and validate the effectiveness of the proposed technique. The proposed 26.2-30 GHz RTWO is implemented in 22 nm fully-depleted silicon-on-insulator (FD-SOI) CMOS for multi-phase clock generation featuring an ultra-low flicker PN corner. At 30 GHz, it achieves PN of -107.6 and -128.9 dBc/Hz at 1 MHz and 10 MHz offsets, respectively. This translates into figures-of-merit (FoMs) of 184.2 and 185.4 dB, for a single-phase, respectively. The proposed architecture consumes 20 mW from a 0.8 V supply. It achieves best-in-class performance with a flicker noise corner of 180 kHz, which is an order of magnitude better than currently reported among RTWOs. Next, a new technique is devised to implement a 32-42 GHz frequency quadrupler that performs digital logic operations between four phase-shifted differential signals at one-fourth of the output frequency. The four phase-shifted signals are generated by a 10 GHz RTWO and are symmetrically routed to the quadrupler using a CMOS buffered clock tree. The harmonic rejection ratio (HRR) is enhanced by employing a differential LC filter tuned at its output center frequency. The proposed frequency quadrupler is implemented in 22 nm FD-SOI CMOS. At 37 GHz, it produces an output power of -4 dBm with a 10% drain efficiency. It consumes 4 mW from a 0.8 V supply and occupies a core area of 0.021 mm2. The worst-case HRR for the fundamental, second, third, and fifth harmonics is 41.3, 48.6, 41.3, and 37.3 dBc, respectively. The DC-to-RF efficiency is better than what can be potentially achieved by other quadrupling techniques. Finally, a 10 GHz RTWO with 32 differential phases was demonstrated. It can act as a DCO and PDC simultaneously, thus simplifying the targeted ADPLL architecture while maintaining an excellent PN. The proposed 8.1-10.3 GHz RTWO is also implemented in 22 nm FD-SOI CMOS. It is digitally tuned using the non-uniform distributed frequency tuning technique to achieve an average frequency resolution of 750 kHz/LSB. The PDC with 32 embedded phases achieves a time resolution of 1.5-1.9 ps. The proposed architecture consumes 30.4 mW from a 0.8 V supply. At 9.3 GHz, it achieves PN of -113.3 and -133.9 dBc/Hz at 1 MHz and 10 MHz offsets, respectively. This corresponds to FoMs of 177.3 and 178 dB, for a single-phase, respectively

Phenotypic identification and antifungal susceptibility patterns of Candida species isolated from various clinical specimens in Suez Canal University Hospitals

Background:  Candida is the most common cause of fungal infections. Candida species are identified by different phenotypic methods. Accurate identification of Candida species enables appropriate selection of antifungal agents by clinicians. Azoles are the most frequently used antifungal drugs to treat Candida infections. However, resistance among previously susceptible Candida species has emerged which made antifungal susceptibility testing crucial. Aim: This study aimed to phenotypically identify the different Candida species isolated from various clinical specimens in Suez Canal University Hospitals (SCUHs), and to assess their antifungal susceptibility patterns. Method: One hundred and five clinical specimens were collected from different departments in SCUHs. Isolates were identified as Candida by colony morphology on Sabouraud dextrose agar and Gram staining. Candida species were phenotypically identified using germ tube test, hypertonic Sabouraud broth, corn meal agar, chromogenic Candida agar, KB006 HiCandida Identification Kit and Vitek 2 YST-ID system. Antifungal susceptibility to fluconazole, voriconazole and amphotericin B was done by disk diffusion method. Results: Prevalence of Candida was 54.3%. C. tropicalis was the most common species followed by C. albicans, C. dubliniensis, C. glabrata, C. parapsilosis and lastly C. kefyr. Only one strain was resistant to amphotericin B. Eight strains were susceptible dose dependent, and 2 were resistant to fluconazole. No resistance was detected to voriconazole. Conclusions: The prevalence of candidiasis is remarkable. Non-albicans Candida species (NACs) cause most of these infections. Fluconazole and amphotericin B showed low resistance rates. No resistance to voriconazole was reported in this study. Therefore, voriconazole could be more effective as empirical therapy than fluconazole and amphotericin B. Accurate identification of Candida species is essential for therapeutic and prognostic impact, appropriate selection of antifungal agents by clinicians and controlling the increase of resistant Candida strains

Comparison between the Standardized Clinical and Laboratory Standards Institute M38-A2 Method and a 2,3-Bis(2-Methoxy-4-Nitro-5-[(Sulphenylamino)Carbonyl]-2H-Tetrazolium Hydroxide- Based Method for Testing Antifungal Susceptibility of Dermatophytes ▿

In this study, we determined the utility of a 2,3-bis(2-methoxy-4-nitro-5-[(sulfenylamino)carbonyl]-2H-tetrazolium hydroxide (XTT)-based assay for determining antifungal susceptibilities of dermatophytes to terbinafine, ciclopirox, and voriconazole in comparison to the Clinical and Laboratory Standards Institute (CLSI) M38-A2 method. Forty-eight dermatophyte isolates, including Trichophyton rubrum (n = 15), Trichophyton mentagrophytes (n = 7), Trichophyton tonsurans (n = 11), and Epidermophyton floccosum (n = 13), and two quality control strains, were tested. In the XTT-based method, MICs were determined spectrophotometrically at 490 nm after addition of XTT and menadione. For the CLSI method, the MICs were determined visually. With T. rubrum, the XTT assay revealed MIC ranges of 0.004 to >64 μg/ml, 0.125 to 0.25 μg/ml, and 0.008 to 0.025 μg/ml for terbinafine, ciclopirox, and voriconazole, respectively. Similar MIC ranges were obtained against T. rubrum by using the CLSI method. Additionally, when tested with T. mentagrophytes, T. tonsurans, and E. floccosum isolates, the XTT and CLSI methods resulted in comparable MIC ranges. Both methods revealed similar lowest drug concentrations that inhibited 90% of the isolates for the majority of tested drug-dermatophyte combinations. The levels of agreement within 1 dilution between both methods were as follows: 100% with terbinafine, 97.8% with ciclopirox, and 89.1% with voriconazole. However, the agreement within 2 dilutions between these two methods was 100% for all tested drugs. Our results revealed that the XTT assay can be a useful tool for antifungal susceptibility testing of dermatophytes