Clinical outcomes of ovarian stimulation with follitropin delta in a mixed regimen with HP-hMG: a real-world retrospective analysise.

INTRODUCTION: Optimising controlled ovarian stimulation (COS) procedures for in vitro fertilisation (IVF) requires an assessment of the patients' medical history, ovarian reserve, prognostic factors and resources to personalise the treatment plan. Treatment personalisation in IVF is increasingly recognised as being vital in providing a balance of efficacy and safety for patients undergoing the COS procedure. In this study, we aimed to assess the efficacy of an ovarian stimulation protocol employing a personalised dosing algorithm for a novel recombinant FSH (rFSH) derived from a human cell-line - follitropin delta, in a mixed gonadotrophin regimen with human menotrophin (HP-HMG). The main outcome of interest in this study is clinical pregnancy rate (CPR) per embryo transfer cycle. MATERIALS AND METHODS: In this single-centre, retrospective, non-interventional study of 20 infertility patients, each individual was provided with a personalised COS regimen based on her ovarian reserve biomarker-serum anti- Mullerian hormone (AMH) and body weight, in a gonadotrophin-receptor hormone (GnRH) antagonist protocol. Personalised dosing of follitropin delta was coadministered with 75 IU of HP-hMG during the COS duration until the final oocyte maturation trigger injection. Ovarian response, pregnancy and safety outcomes resulting from this procedure were assessed and reported here. RESULTS: Following a mean COS duration of 11 days and 50% of patients who underwent frozen embryo transfers, the CPR per started cycle was 70%. The observed CPR from this study was higher than that reported in the follitropin delta Phase 3 studies using rFSH monotherapy stimulation, and additionally showed no incidents of cycle cancellations and no iatrogenic safety risks such as ovarian hyperstimulation syndrome. CONCLUSION: The present study provides a first glimpse into the favourable benefit: risk profile of a mixed protocol regimen using follitropin delta combined with HP-hMG in a cohort of Asian patients in Malaysia.

N95 respirator decontamination: a study in reusability.

The coronavirus disease 2019 (COVID-19) pandemic had caused a severe depletion of the worldwide supply of N95 respirators. The development of methods to effectively decontaminate N95 respirators while maintaining their integrity is crucial for respirator regeneration and reuse. In this study, we systematically evaluated five respirator decontamination methods using vaporized hydrogen peroxide (VHP) or ultraviolet (254 nm wavelength, UVC) radiation. Through testing the bioburden, filtration, fluid resistance, and fit (shape) of the decontaminated respirators, we found that the decontamination methods using BioQuell VHP, custom VHP container, Steris VHP, and Sterrad VHP effectively inactivated Cardiovirus (3-log10 reduction) and bacteria (6-log10 reduction) without compromising the respirator integrity after 2-15 cycles. Hope UVC system was capable of inactivating Cardiovirus (3-log10 reduction) but exhibited relatively poorer bactericidal activity. These methods are capable of decontaminating 10-1000 respirators per batch with varied decontamination times (10-200 min). Our findings show that N95 respirators treated by the previously mentioned decontamination methods are safe and effective for reuse by industry, laboratories, and hospitals.

Optimal Scree-CNN for Detecting NS1 Molecular Fingerprint from Salivary SERS Spectra.

Dengue fever (DF) is a viral infection with possible fatal consequence. NS1 is a recent antigen based biomarker for dengue fever (DF), as an alternative to current serum and antibody based biomarkers. Convolutional Neural Network (CNN) has demonstrated impressive performance in machine learning problems. Our previous research has captured NS1 molecular fingerprint in saliva using Surface Enhanced Raman Spectroscopy (SERS) with great potential as an early, noninvasive detection method. SERS is an enhanced variant of Raman spectroscopy, with extremely high amplification that enables spectra of low concentration matter, such as NS1 in saliva, readable. The spectrum contains 1801 features per sample, at a total of 284 samples. Principal Component Analysis (PCA) transforms high dimensional correlated signal to a lower dimension uncorrelated principal components (PCs), at no sacrifice of the original signal content. This paper aims to unravel an optimal Scree-CNN model for classification of salivary NS1 SERS spectra. Performances of a total of 490 classifier models were examined and compared in terms of performance indicators [accuracy, sensitivity, specificity, precision, kappa] against a WHO recommended clinical standard test for DF, enzyme-linked immunosorbent assay (ELISA). Effects of CNN parameters on performances of the classifier models were also observed. Results showed that Scree-CNN classifier model with learning rate of 0.01, mini-batch size of 64 and validation frequency of 50, reported an across-the-board 100% for all performance indicators.

New Service Model for Common Mental Disorders in Hong Kong: a Retrospective Outcome Study.

OBJECTIVE: To review the first 8-month outcome of the Common Mental Disorder Clinic model in Hong Kong in terms of patient exit status and improvement in depressive and anxiety symptoms. METHODS: During the first appointment, patients were interviewed by a multidisciplinary team comprising a psychiatrist, a psychiatric nurse, and an occupational therapist. A multidisciplinary case conference was conducted to discuss clinical observations, diagnosis, issues of concern, and the optimal individualised treatment plan. Low-intensity interventions by nurses and/or occupational therapists were provided, as were optional, time-limited, protocol-based interventions by clinical psychologists for those with mild to moderate depressive and anxiety symptoms. Pharmacological intervention may be used when indicated. Upon completion of the treatment plan, patients were reassessed by the treating psychiatrist. Discharge options included discharge without psychiatric follow-up, step-up to psychiatric outpatient clinics, and step-down services. The self-administered Patient Health Questionnaire-9 (PHQ-9) and Generalised Anxiety Disorder 7-item scale (GAD-7) were used to assess the past 2 weeks' depressive and anxiety symptoms, respectively, at baseline and at each session. RESULTS: From July 2015 to February 2016, 1325 Chinese patients received the new service. Of them, 170 men and 363 women (mean age, 52.6 years) completed the treatment plan. After treatment, their mean PHQ-9 score decreased from 11.06 to 7.55 (p < 0.001), and the mean GAD-7 score decreased from 9.94 to 6.54 (p < 0.001). After treatment, 42.4% and 48.2% of the patients were within the normal range of PHQ-9 and GAD-7 scores, respectively, compared with 16.9% and 20.8% before treatment. The mean time to implementation of the individualised treatment plan was 82.33 days. Of the patients, 54.4% were discharged without any need for medical or psychiatric follow-up; 28% were stepped up to psychiatric outpatient clinics; and 17.3% were stepped down. The predictors of exit status were whether psychiatric medication was prescribed during initial intake (p = 0.011), whether psychiatric medication was prescribed at last follow-up (p < 0.001), the service period (p = 0.010), and the GAD-7 final score (p = 0.005). CONCLUSIONS: The first 8-month outcome of the new service model was encouraging, with shortened waiting time, reduced severity of symptoms, and better exit status (high recovery and step-down rates).

Coronary artery hypoxic vasorelaxation is augmented by perivascular adipose tissue through a mechanism involving hydrogen sulphide and cystathionine-ß-synthase.

AIM: Hypoxia causes vasodilatation of coronary arteries which protects the heart from ischaemic damage through mechanisms including the generation of hydrogen sulphide (H2 S), but the influence of the perivascular adipose tissue (PVAT) and myocardium is incompletely understood. This study aimed to determine whether PVAT and the myocardium modulate the coronary artery hypoxic response and whether this involves hydrogen sulphide. METHODS: Porcine left circumflex coronary arteries were prepared as cleaned segments and with PVAT intact, myocardium intact or both PVAT and myocardium intact, and contractility investigated using isometric tension recording. Immunoblotting was used to measure levels of H2 S-synthesizing enzymes: cystathionine-ß-synthase (CBS), cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulphurtransferase (MPST). RESULTS: All three H2 S-synthesizing enzymes were detected in the artery and myocardium, but only CBS and MPST were detected in PVAT. Hypoxia elicited a biphasic response in cleaned artery segments consisting of transient contraction followed by prolonged relaxation. In arteries with PVAT intact, hypoxic contraction was attenuated and relaxation augmented. In arteries with myocardium intact, hypoxic contraction was attenuated, but relaxation was unaffected. In replacement experiments, replacement of dissected PVAT and myocardium attenuated artery contraction and augmented relaxation to hypoxia, mimicking the effect of in situ PVAT and indicating involvement of a diffusible factor(s). In arteries with intact PVAT, augmentation of hypoxic relaxation was reversed by amino-oxyacetate (CBS inhibitor), but not DL-propargylglycine (CSE inhibitor) or aspartate (inhibits MPST pathway). CONCLUSION: PVAT augments hypoxic relaxation of coronary arteries through a mechanism involving H2 S and CBS, pointing to an important role in regulation of coronary blood flow during hypoxia.

PCA-MLP SVM distinction of salivary Raman spectra of dengue fever infection.

Dengue fever (DF) is a disease of major concern caused by flavivirus infection. Delayed diagnosis leads to severe stages, which could be deadly. Of recent, non-structural protein (NS1) has been acknowledged as a biomarker, alternative to immunoglobulins for early detection of dengue in blood. Further, non-invasive detection of NS1 in saliva makes the approach more appealing. However, since its concentration in saliva is less than blood, a sensitive and specific technique, Surface Enhanced Raman Spectroscopy (SERS), is employed. Our work here intends to define an optimal PCA-SVM (Principal Component Analysis-Support Vector Machine) with Multilayer Layer Perceptron (MLP) kernel model to distinct between positive and negative NS1 infected samples from salivary SERS spectra, which, to the best of our knowledge, has never been explored. Salivary samples of DF positive and negative subjects were collected, pre-processed and analyzed. PCA and SVM classifier were then used to differentiate the SERS analyzed spectra. Since performance of the model depends on the PCA criterion and MLP parameters, both are examined in tandem. Its performance is also compared to our previous works on simulated NS1 salivary samples. It is found that the best PCA-SVM (MLP) model can be defined by 95 PCs from CPV criterion with P1 and P2 values of 0.01 and -0.2 respectively. A classification performance of [76.88%, 85.92%, 67.83%] is achieved.

A critical role for cystathionine-ß-synthase in hydrogen sulfide-mediated hypoxic relaxation of the coronary artery.

Hypoxia-induced coronary artery vasodilatation protects the heart by increasing blood flow under ischemic conditions, however its mechanism is not fully elucidated. Hydrogen sulfide (H2S) is reported to be an oxygen sensor/transducer in the vasculature. The present study aimed to identify and characterise the role of H2S in the hypoxic response of the coronary artery, and to define the H2S synthetic enzymes involved. Immunoblotting and immunohistochemistry showed expression of all three H2S-producing enzymes, cystathionine-ß-synthase (CBS), cystathionine-γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (MPST), in porcine coronary artery. Artery segments were mounted for isometric tension recording; hypoxia caused a transient endothelium-dependent contraction followed by prolonged endothelium-independent relaxation. The CBS inhibitor amino-oxyacetate (AOAA) reduced both phases of the hypoxic response. The CSE inhibitor dl-propargylglycine (PPG) and aspartate (limits MPST) had no effect alone, but when applied together with AOAA the hypoxic relaxation response was further reduced. Exogenous H2S (Na2S and NaHS) produced concentration-dependent contraction followed by prolonged relaxation. Responses to both hypoxia and exogenous H2S were dependent on the endothelium, NO, cGMP, K+ channels and Cl-/HCO3- exchange. H2S production in coronary arteries was blocked by CBS inhibition (AOAA), but not by CSE inhibition (PPG). These data show that H2S is an endogenous mediator of the hypoxic response in coronary arteries. Of the three H2S-producing enzymes, CBS, expressed in the vascular smooth muscle, appears to be the most important for H2S generated during hypoxic relaxation of the coronary artery. A contribution from other H2S-producing enzymes only becomes apparent when CBS activity is inhibited.

Filariasis in axillary lymph node.

A case of adult filarial worms detected in an axillary lymph node of an asymptomatic patient. A 64 year-old Indian female underwent a mammogram and was incidentally found to have punctate microcalcifications in the upper outer quadrant of the left breast with left axillary lymphadenopathy. She has underlying hypertension and diabetes mellitus on oral medications. She has no family history of breast malignancy. Fine needle aspiration of the left axillary lymph node was suggestive of reactive lympha-denitis. Histopathological examination of excisional biopsy of left breast lump showed fibrocystic disease; no evidence of malignancy was detected whereas excisional biopsy of left axillary lymph node showed reactive lymphoid hyperplasia, featuring variably sized lymphoid follicles with intact mantle zone. No expansion of marginal zone was noted. Occasional pigment-laden macrophages were seen. One of the lymph node showed presence of calcified serpinginous tubular bodies, in keeping with non viable parasite organisms with intact outlines of the structures. There were no eosinophilic infiltrates. The possibility of filarial infestation was suspected. Histopathological sample was sent for further identification and confirmed the presence of adult filarial worm.

Suppression of peptide ion dissociation under electron capture: role of backbone amide hydrogen.

RATIONALE: The electron capture dissociation (ECD) of proteins/peptides is affected by the nature and sequence of amino acid residues. Electron capture/transfer with no dissociation is an intriguing phenomenon that has occasionally been observed. We have previously identified that diarginated peptides enriched with glutamic acid residues were found to show suppression of backbone fragmentation. In this paper, we report the effect of geometrical parameters of a peptide, including chain length, conformation and amide hydrogen, on the suppression of ECD fragmentation using synthetic model peptides. METHODS: Glycine containing model polypeptides were used to probe the mechanism. Molecular-mechanics was used to obtain the conformation of the precursor ions. The ECD experiments were performed on a Bruker APEX III 4.7 T Fourier transform ion cyclotron resonance (FTICR) mass spectrometer. RESULTS: Significant decreases in the intensities of the fragment ions were observed for the 23-mer polypeptide with only one E residue. This implied that the E:R ratio was no longer the sole determining factor for the occurrence of suppression effects. Results of conformational searches showed that there was a hydrogen-bonding 'ladder' formed in the 23-mer polypeptide, which was not found in the 15-mer peptide. Substituting the normal amino acid residues by the corresponding N-methylated amino acid residues in the model peptide, the suppression effect disappeared. CONCLUSIONS: Our results indicate that survival of the intact reduced peptide ion after electron capture depends also on the length of the peptide. The amide hydrogen was critical in forming the resonance structure that suppressed the ECD fragmentation.

A role for the sodium pump in H2O2-induced vasorelaxation in porcine isolated coronary arteries.

Hydrogen peroxide (H2O2) has been proposed to act as a factor for endothelium-derived hyperpolarization (EDH) and EDH may act as a 'back up' system to compensate the loss of the NO pathway. Here, the mechanism of action of H2O2 in porcine isolated coronary arteries (PCAs) was investigated. Distal PCAs were mounted in a wire myograph and pre-contracted with U46619 (1nM-50µM), a thromboxane A2-mimetic or KCl (60mM). Concentration-response curves to H2O2(1µM-1mM), bradykinin (0.01nM-1µM), sodium nitroprusside (SNP) (10nM-10µM), verapamil (1nM-10µM), KCl (0-20mM) or Ca(2+)-reintroduction (1µM-10mM) were constructed in the presence of various inhibitors. Activity of the Na(+)/K(+)-pump was measured through rubidium-uptake using atomic absorption spectrophotometry. H2O2 caused concentration-dependent vasorelaxations with a maximum relaxation (Rmax) of 100±16% (mean±SEM), pEC50=4.18±0.20 (n=4) which were significantly inhibited by PEG-catalase at 0.1-1.0mM H2O2 (P<0.05). 10mM TEA significantly inhibited the relaxation up to 100µM H2O2 (P<0.05). 60mM K(+) and 500nM ouabain significantly inhibited H2O2-induced vasorelaxation producing a relaxation of 40.8±8.5% (n=5) and 47.5±8.6% (n=6) respectively at 1mM H2O2 (P<0.0001). H2O2-induced vasorelaxation was unaffected by the removal of endothelium, inhibition of NO, cyclo-oxygenase, gap junctions, SKCa, IKCa, BKCa Kir, KV, KATP or cGMP. 100µM H2O2 had no effects on the KCl-induced vasorelaxation or Ca(2+)-reintroduction contraction. 1mM H2O2 inhibited both KCl-induced vasorelaxation and rubidium-uptake consistent with inhibition of the Na(+)/K(+)-pump activity. We have shown that the vascular actions of H2O2 are sensitive to ouabain and high concentrations of H2O2 are able to modulate the Na(+)/K(+)-pump. This may contribute towards its vascular actions.

Identification and in vitro antimicrobial susceptibility of Brucella species isolated from human brucellosis.

Brucellosis is a world-wide zoonotic disease with a major impact on the public health. Due to the high risk of laboratory acquired infection, limited laboratory investigations were performed on this organism, including detailed identification and susceptibility study. Brucella melitensis is the commonest aetiological agent for human brucellosis in this region. The in vitro susceptibility pattern against selected antimicrobial agents was assessed using E-test. All isolates were noted to be sensitive to all the antimicrobial agents tested except for rifampicin where elevated MIC > 1 µg/mL was noted in 30 out of 41 isolates tested.

Sex differences in endothelial function in porcine coronary arteries: a role for H2O2 and gap junctions?

BACKGROUND AND PURPOSE: Cardiovascular risk is higher in men and postmenopausal women compared with premenopausal women. This may be due to sex differences in endothelial function. Here, sex differences in endothelial function of porcine coronary arteries (PCAs) were investigated. EXPERIMENTAL APPROACH: Distal PCAs were studied under myographic conditions and after precontraction with U46619. Concentration-response curves to bradykinin were constructed in the presence of a range of inhibitors. KEY RESULTS: In male and female PCAs, bradykinin produced comparable vasorelaxant responses. Inhibition of NO and prostanoid synthesis produced greater inhibition in males compared with females. Removing H2 O2 with PEG-catalase reduced the maximum relaxation in the absence, but not the presence of L-NAME and indomethacin in females, and had no effect in males. Blocking gap junctions with 100 µM carbenoxolone or 18α-glycyrrhetinic acid further inhibited the endothelium-derived hyperpolarization (EDH)-mediated response in females but not in males. In female PCAs, the maximum EDH-mediated response was reduced by inhibiting SKCa with apamin and by inhibiting IKCa with TRAM-34, or with both. In male PCAs, at maximum bradykinin concentration, the EDH-mediated response was reduced in the presence of apamin but not TRAM-34. Western blot did not detect any differences in connexins 40 or 43 or in IKCa expression between male and female PCAs. CONCLUSIONS AND IMPLICATIONS: H2 O2 mediated some part of endothelium-dependent vasorelaxation in female PCAs and EDH was more important in females, with differences in the contribution of gap junctions and IKCa channels. These findings may contribute to understanding vascular protection in premenopausal women.

Clinicians' knowledge, beliefs and acceptance of intravenous-to-oral antibiotic switching, Hospital Pulau Pinang.

A cross-sectional study was conducted to explore clincians' baseline knowledge, practice beliefs and acceptance of intravenous (IV)-to-oral antibiotic switching practice in Hospital Pulau Pinang. The factors most highly rated for antibiotic conversion were the ability to maintain oral intake (85.6%) and microbiology etiology (85.0%). Majority of the clinicians (76%) agreed with the traditional clinical rule that "patient should be afebrile for 24 hours before IV-to-oral switch". Specialists and consultants had the highest knowledge score among the clinicians. However, they were generally less positive about a guideline being integrated into practice.

Clinically important detection of infection as an 'incidental' finding during cancer staging using FDG-PET/CT.

BACKGROUND: FDG-PET/CT is widely used in the management of a variety of malignancies with excellent overall accuracy, despite the potential for false positive results related to infection and inflammation. AIM: As cancer patients can develop clinically inapparent infections, we evaluated the prevalence and nature of incidental findings reported to be suggestive of infections that had been identified during clinical cancer staging with FDG-PET/CT. METHODS: The study involved a retrospective analysis of 60 patients managed primarily at our facility from a total of 121 cases identified as having possible infection on clinical reporting of more than 4500 cancer staging investigations performed during the calendar year of 2008. RESULTS: Occult infections were uncommon overall (≤1%), but most often because of pneumonia (31.6%), upper respiratory tract infections (21.1%) or wound infections (15.8%). Abnormal scans contributed to patients' management in 52.7% of cases. Two out of 13 patients whose scan abnormalities were not investigated further had worsening changes on repeated scan and one of these patients had clinical deterioration. CONCLUSIONS: In patients with FDG-PET/CT scans suggestive of infection and in whom a final diagnosis could be reached, the positive predictive value for FDG-PET/CT scans was 89% suggesting that abnormal scans indicative of infection should be investigated further in this population.

Effectiveness of coordination exercise in improving cognitive function in older adults: a prospective study.

BACKGROUND: Studies on the effect of a low intensity coordination exercise on the elderly with limited mobility are sparse. This prospective study attempted to compare the effectiveness of a customized coordination exercise and a strength exercise in improving the cognitive functioning and physical mobility on the elderly. METHODS: Participants from two centers for the elderly were allocated to practice either an 8-week coordination training (CT) program or an 8-week towel exercise (TE) program. The Chinese Mini-Mental State Examination and Chinese Dementia Rating Scale (CDRS) were used to measure cognitive functioning of participants, and Timed Up-and-Go test for physical mobility. These assessments were administered before and after the program. RESULTS: Paired t-tests showed that the CDRS scores of the CT group improved significantly from 114.8 at pre-test to 119.3 after training (P = 0.045). The CDRS scores of the TE group also improved from 114.9 at pre-test to 116.9 after training. CONCLUSION: Findings from this prospective study demonstrated that low-intensity level mind-body exercise could be beneficial to the cognitive functioning of older adults.

Lateral interdot carrier transfer in an InAs quantum dot cluster grown on a pyramidal GaAs surface.

InAs quantum dot clusters (QDCs), which consist of three closely spaced QDs, are formed on nano-facets of GaAs pyramidal structures by selective-area growth using metal-organic chemical vapor deposition. Photoluminescence (PL) and time-resolved PL (TRPL) experiments, measured in the PL linewidth, peak energy and QD emission dynamics indicate lateral carrier transfer within QDCs with an interdot carrier tunneling time of 910 ps under low excitation conditions. This study demonstrates the controlled formation of laterally coupled QDCs, providing a new approach to fabricate patterned QD molecules for optical computing applications.

Fabrication and characteristics of broad-area light-emitting diode based on nanopatterned quantum dots.

The device fabrication and integration of nanopatterned quantum dots (PQDs) are realized through the demonstration of a broad-area light-emitting diode with PQD active region. The device involves two growth processes, first to form PQDs by selective-area epitaxy on an SiO(2) mask and then to complete the device structure after mask removal. Linear current-voltage characteristics are observed with sharp turn-on, low leakage current and low forward resistance. Electroluminescence spectra show PQD intraband structure and low quenching of emission from 77 K to room temperature. Light-current measurements demonstrate external quantum efficiency per PQD comparable to self-assembled QDs, thus providing a possible route toward individually addressable single QD devices.

Improved photoluminescence efficiency of patterned quantum dots incorporating a dots-in-the-well structure.

InAs quantum dots embedded in InGaAs quantum well (DWELL: dots-in-the-well) structures grown on nanopatterned GaAs pyramids and planar GaAs(001) surface are comparatively investigated. Photoluminescence (PL) measurements demonstrate that the DWELL structure grown on the GaAs pyramids exhibits a broad quantum well PL band (full width at half-maximum ∼ 90 meV) and a higher quantum dot emission efficiency than the DWELL structure grown on the planar GaAs(001) substrate. These properties are attributed to the InGaAs quantum well with distributed thickness profile on the faceted GaAs pyramids, which introduces a tapered energy band structure and enhances carrier capture into the quantum dots.