Women in Orthopaedics: A Perspective from Malaysian Female Orthopaedic Surgeons.

Introduction: The awareness of under-representation of female surgeons in orthopaedics has been increasing in this decade. We aim to investigate the reasons why female surgeons chose orthopaedic, the barriers that possibly hinder female surgeons into orthopaedics and analyse the obstacles that they encountered in their career in Malaysian context. Materials and methods: A total of 101 registered female orthopaedic surgeons registered with the Malaysian Medical Council, during the period 1980 to 2020, were contacted for a cross-sectional survey, consisting of thirty-four questions on their experience in the orthopaedic career. Eighty-two responses were received (81.2%). Questions in this survey consisted of four sections: (1) demographic details, (2) current clinical practice environment, (3) orthopaedics training experience, and (4) career experience. Results: A total of 49% of respondents had subspeciality training, highest in paediatric orthopaedic (30%). Enjoyment of manual tasks (64.6%) and professional satisfaction (64.6%) were the top reasons for choosing orthopaedic as a career. Primary barriers to orthopaedic were physical strength required (56.0%) and public gender bias (52.4%). Twenty-eight percent reported gender discrimination in career opportunities while 60% reported similar in daily work. Thirty-three percent reported verbal and 11% physical sexual harassment in their career. Forty-four percent of respondents reported benefits as female orthopaedic surgeon in their work. Conclusion: The reasons for Malaysian female orthopaedic surgeons to choose orthopaedic as their career and the barriers perceived to hinder other females from choosing orthopaedics were similar to reports worldwide with no exception to gender discrimination and sexual harassment. The support given by male colleagues to married female surgeons marked a unique phenomenon in Malaysian culture.

Foot Arch Changes after Endoscopic Plantar Fascia Release for Recalcitrant Plantar Fasciitis.

Introduction: Endoscopic plantar fascia release (EPFR) is a minimally invasive surgical intervention for recalcitrant plantar fasciitis. Its efficacy has been convincing but the in vivo effect on medial longitudinal foot arch and footprint has not been studied. Our objective is to evaluate the changes of foot posture using radiographs and footprints following endoscopic plantar fascia release in recalcitrant plantar fasciitis. Materials and methods: This prospective cohort involved patients with recalcitrant plantar fasciitis who failed six months of conservative treatment. Two-portal endoscopic release of not more than 50% of plantar fascia width was performed. Footprint and standard weight-bearing anteroposterior and lateral radiographs of the foot were taken pre-operatively and at 12 months post-surgery. Arch index, normalised navicular height truncated, calcaneal inclination angle, calcano-1st metatarsal angle, talonavicular coverage angle and talus-2nd metatarsal angle were measured. Results: Sixteen patients (18 feet) were reported. Patients' follow-up ranged from 14 to 31 months after surgery (mean±SD: 23.44±5.76). The increase of arch index, calcano-1st metatarsal angle and reduction of calcaneal inclination angle were found statistically significant (p<0.05). Two normal arch patients progressed to asymptomatic flat arch feet. Three complications were noted between three to nine months post-surgery, one with medial column and two with lateral column symptoms. Conclusion: There is evidence of reduction in medial longitudinal arch of the foot after EPFR. Although the reduction remains asymptomatic, post-operative complications related to changes in biomechanics of the foot can occur between three to nine months. Patients should be monitored at least for 12 months and longer for those who are symptomatic.

Natural DENV-2 NS2B/NS3 protease inhibitors from Myristica cinnamomea King.

The NS2B/NS3 protease is crucial for the pathogenesis of the DENV. Therefore, the inhibition of this protease is considered to be the key strategy for the development of new antiviral drugs. In the present study, malabaricones C (3) and E (4), acylphenols from the fruits of Myristica cinnamomea King, have been respectively identified as moderate (27.33 ± 5.45 µM) and potent (7.55 ± 1.64 µM) DENV-2 NS2B/NS3 protease inhibitors, thus making this the first report on the DENV-2 NS2B/NS3 protease inhibitory activity of acylphenols. Based on the molecular docking studies, compounds 3 and 4 both have π-π interactions with Tyr161. While compound 3 has hydrogen bonding interactions with Gly151, Gly153 and Tyr161, compound 4 however, forms hydrogen bonds with Ser135, Asp129, Phe130 and Ile86 instead. The results from the present study suggests that malabaricones C (3) and E (4) could be employed as lead compounds for the development of new dengue antivirals from natural origin.

Enhancement of semantic integration reasoning by tRNS.

The right hemisphere is involved with the integrative processes necessary to achieve global coherence during reasoning and discourse processing. Specifically, the right temporal lobe has been proven to facilitate the processing of distant associate relationships, such as generating novel ideas. Previous studies showed a specific swing of alpha and gamma oscillatory activity over the right parieto-occipital lobe and the right anterior temporal lobe respectively, when people solve semantic problems with a specific strategy, i.e., insight problem-solving. In this study, we investigated the specificity of the right parietal and temporal lobes for semantic integration using transcranial Random Noise Stimulation (tRNS). We administered a set of pure semantics (i.e., Compound Remote Associates [CRA]) and visuo-semantic problems (i.e., Rebus Puzzles) to a sample of 31 healthy volunteers. Behavioral results showed that tRNS stimulation over the right temporal lobe enhances CRA accuracy (+12%), while stimulation on the right parietal lobe causes a decrease of response time on the same task (-2,100 ms). No effects were detected for Rebus Puzzles. Our findings corroborate the involvement of the right temporal and parietal lobes when solving purely semantic problems but not when they involve visuo-semantic material, also providing causal evidence for their postulated different roles in the semantic integration process and promoting tRNS as a candidate tool to boost verbal reasoning in humans.

Natural DENV-2 NS2B/NS3 protease inhibitors from Myristica cinnamomea King

@#The NS2B/NS3 protease is crucial for the pathogenesis of the DENV. Therefore, the inhibition of this protease is considered to be the key strategy for the development of new antiviral drugs. In the present study, malabaricones C (3) and E (4), acylphenols from the fruits of Myristica cinnamomea King, have been respectively identified as moderate (27.33 ± 5.45 μM) and potent (7.55 ± 1.64 μM) DENV-2 NS2B/NS3 protease inhibitors, thus making this the first report on the DENV-2 NS2B/NS3 protease inhibitory activity of acylphenols. Based on the molecular docking studies, compounds 3 and 4 both have π-π interactions with Tyr161. While compound 3 has hydrogen bonding interactions with Gly151, Gly153 and Tyr161, compound 4 however, forms hydrogen bonds with Ser135, Asp129, Phe130 and Ile86 instead. The results from the present study suggests that malabaricones C (3) and E (4) could be employed as lead compounds for the development of new dengue antivirals from natural origin.

COVID-19: Four Paediatric Cases in Malaysia.

OBJECTIVE: This is a brief report of 4 paediatric cases of COVID-19 infection in Malaysia BACKGROUND: COVID-19, a coronavirus, first detected in Wuhan, China has now spread rapidly to over 60 countries and territories around the world, infecting more than 85000 individuals. As the case count amongst children is low, there is need to report COVID-19 in children to better understand the virus and the disease. CASES: In Malaysia, until end of February 2020, there were four COVID-19 paediatric cases with ages ranging from 20 months to 11 years. All four cases were likely to have contracted the virus in China. The children had no symptoms or mild flu-like illness. The cases were managed symptomatically. None required antiviral therapy. DISCUSSION: There were 2 major issues regarding the care of infected children. Firstly, the quarantine of an infected child with a parent who tested negative was an ethical dilemma. Secondly, oropharyngeal and nasal swabs in children were at risk of false negative results. These issues have implications for infection control. Consequently, there is a need for clearer guidelines for child quarantine and testing methods in the management of COVID-19 in children.

The global prevalence of multidrug-resistance among Acinetobacter baumannii causing hospital-acquired and ventilator-associated pneumonia and its associated mortality: A systematic review and meta-analysis.

OBJECTIVE: The objective of this works was to assess the global prevalence of multidrug-resistance among A. baumannii causing hospital-acquired (HAP) and ventilator-associated pneumonia (VAP), and describe its associated mortality. METHODS: We performed a systematic search of four databases for relevant studies. Meta-analysis was done based on United Nations geoscheme regions, individual countries and study period. We used a random-effects model to calculate pooled prevalence and mortality estimates with 95% confidence intervals (CIs), weighted by study size. RESULTS: Among 6445 reports screened, we identified 126 relevant studies, comprising data from 29 countries. The overall prevalence of multidrug-resistance among A. baumannii causing HAP and VAP pooled from 114 studies was 79.9% (95% CI 73.9-85.4%). Central America (100%) and Latin America and the Caribbean (100%) had the highest prevalence, whereas Eastern Asia had the lowest (64.6%; 95% CI, 50.2-77.6%). The overall mortality estimate pooled from 27 studies was 42.6% (95% CI, 37.2-48.1%). CONCLUSIONS: We observed large amounts of variation in the prevalence of multidrug-resistance among A. baumannii causing HAP and VAP and its mortality rate among regions and lack of data from many countries. Data from this review can be used in the development of customized strategies for infection control and antimicrobial stewardship.

Nurses' knowledge, beliefs and practices regarding the screening and treatment of postpartum depression in maternal and child health clinics: A cross-sectional survey.

BACKGROUND: Postpartum depression (PPD) affects 10-15% of women worldwide, and screening is recommended by clinical guidelines. In Malaysia, nurses in maternal and child health (MCH) clinics provide postpartum care. AIM: To determine nurses' level of knowledge, beliefs and practices regarding PPD and factors associated with screening practices. METHODS: A cross-sectional study using universal sampling was conducted on nurses from seven government MCH clinics in Malaysia. Data was collected from March until April 2016 through a self-reported questionnaire. Univariate and multivariate analyses were performed to identify factors associated with having ever performed PPD screening. RESULTS: Of the 108 nurses, 55.6% scored above the median total knowledge score (17 out of 24 points). Despite a high proportion of nurses believing that they were responsible for PPD screening (72.2%), counselling depressed mothers (72.2%) and referring mothers for further treatment (87.0%), only 64.8% and 51.9% were confident in recognizing PPD and counselling depressed mothers, respectively. Only 25.9% had ever practiced PPD screening, which was associated with beliefs concerning screening taking too much time (adjusted odds ratio [AOR]=0.13, 95% confidence interval [CI]= 0.02-0.74, P=0.022) and that screening is their responsibility (AOR=14.12, 95%CI=1.65-120.75, P=0.016). CONCLUSION: More than half of the nurses scored above the median total knowledge score and had positive beliefs towards PPD screening. However, PPD screening practices were poor, and this outcome was associated with their beliefs regarding time and responsibility.

Cisplatin- and cyclophosphamide-induced primordial follicle depletion is caused by direct damage to oocytes.

It is well established that DNA-damaging chemotherapies can cause infertility and ovarian endocrine failure by depleting the ovarian reserve of primordial follicles. Currently, no effective pharmacological therapies exist for the preservation of long-term fertility and ovarian function in female cancer patients, due to a limited understanding of the mechanisms of chemotherapy-induced follicle depletion. This study investigated the cellular targets, molecular mechanisms, and temporal course of ovarian reserve depletion following treatment with commonly used chemotherapeutic drugs. Adult female C57BL/6 mice were injected i.p. with saline, cisplatin (5mg/kg), or cyclophosphamide (300mg/kg); ovaries were harvested after 8 or 24 hours. Follicle counts showed depletion of all follicular stages 24 hours after administration of cisplatin or cyclophosphamide. Eight hours post-treatment, H2A histone family member X (γH2AX) immunofluorescence showed DNA double-stranded breaks at all follicular stages, including within primordial follicle oocytes. This staining was resolving by 24 hours, indicating that primordial follicle oocytes begin to undergo either apoptosis or repair in this timeframe. γH2AX-positive follicles were further examined to identify the specific cell types damaged. In primordial, transitional, and primary follicles, only oocytes sustained DNA damage, whereas in secondary and antral follicles, only somatic cells were affected. TUNEL staining confirmed that apoptosis occurs in these targeted cell types. Whilst multi-drug and multi-dose regimens were not examined, this study conclusively shows that cyclophosphamide and cisplatin cause direct damage to primordial follicle oocytes, which then undergo apoptosis. Therefore, future pharmacological strategies to prevent chemotherapy-induced infertility in females must specifically prevent primordial follicle oocyte death.

Clinical prediction models for ESBL-Enterobacteriaceae colonization or infection: a systematic review.

BACKGROUND: ß-Lactamase resistance among certain Gram-negative bacteria has been associated with increased mortality, length of hospitalization, and hospital costs. AIM: To identify and critically appraise existing clinical prediction models of extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-EKP) infection or colonization. METHODS: Electronic databases, reference lists, and citations were searched from inception to April 2018. Papers were included in any language describing the development or validation, or both, of models and scores to predict the risk of ESBL-EKP infection or colonization. FINDINGS: In all, 1795 references were screened, of which four articles were included in the review. The included studies were carried out in different geographical locations with differing study designs, and inclusion and exclusion criteria. Most if not all studies lacked external validation and blinding of reviewers during the evaluation of the predictor variables and outcome. All studies excluded missing data and most studies did not report the number of patients excluded due to missing data. Fifteen predictors of infection or colonization with ESBL-EKP were identified. Commonly included predictors were previous antibiotic use, previous hospitalization, transfer from another healthcare facility, and previous procedures (urinary catheterization and invasive procedures). CONCLUSION: Due to limitations and variations in the study design, clinicians would have to take these differences into consideration when deciding on how to use these models in clinical practice. Due to lack of external validation, the generalizability of these models remains a question. Therefore, further external validation in local settings is needed to confirm the usefulness of these models in supporting decision-making.

Dengue protease inhibition activity of selected Malaysian medicinal herbs.

Dengue fever is one of major health problem around the world including Malaysia. It is caused by the arthropode-borne flavivirus and transmitted by the bite of the Aedes aegypti or Aedes albopictus mosquito infected with one of the four dengue virus serotypes (DENV-1, DENV-2, DENV-3, or DENV-4). In this study, a screening exercise of various Malaysian medicinal plants showed that the extracts of Lawsonia inermis, Dryobalanops aromatica, Punica granatum, Zizyphus jujuba Lam. and Zingiber zerumbet exhibited potent inhibitory activity against NS2B-NS3 serine protease. The methanol extracts of Dryobalanops aromatica showed inhibition of 99.70 % at concentration of 200 µg/mL with IC50 value of 0.30 ± 0.16 µg/mL.

Dengue protease inhibition activity of selected Malaysian medicinal herbs

@#Dengue fever is one of major health problem around the world including Malaysia. It is caused by the arthropode-borne flavivirus and transmitted by the bite of the Aedes aegypti or Aedes albopictus mosquito infected with one of the four dengue virus serotypes (DENV-1, DENV-2, DENV-3, or DENV-4). In this study, a screening exercise of various Malaysian medicinal plants showed that the extracts of Lawsonia inermis, Dryobalanops aromatica, Punica granatum, Zizyphus jujuba Lam. and Zingiber zerumbet exhibited potent inhibitory activity against NS2B-NS3 serine protease. The methanol extracts of Dryobalanops aromatica showed inhibition of 99.70 % at concentration of 200 μg/mL with IC50 value of 0.30 ± 0.16 μg/mL.

Relationship between facet joint distraction during anterior cervical discectomy and fusion for trauma and functional outcome.

Aims: The purpose of this retrospective study was to investigate the clinical relevance of increased facet joint distraction as a result of anterior cervical decompression and fusion (ACDF) for trauma. Patients and Methods: A total of 155 patients (130 men, 25 women. Mean age 42.7 years; 16 to 87) who had undergone ACDF between 1 January 2001 and 1 January 2016 were included in the study. Outcome measures included the Neck Disability Index (NDI) and visual analogue scale (VAS) for pain. Lateral cervical spine radiographs taken in the immediate postoperative period were reviewed to compare the interfacet distance of the operated segment with those of the facet joints above and below. Results: There was a statistically significant relationship between greater facet distraction and increased NDI and VAS pain scores. This was further confirmed by Spearman correlation, which showed evidence of a moderate correlation between both NDI score and facet joint distraction (Spearman correlation coefficient 0.34; p < 0.001) and VAS score and facet distraction (Spearman correlation coefficient 0.52; p < 0.001). Furthermore, there was a discernible transition point between outcome scores. Significantly worse outcomes, in terms of both NDI scores (17.8 vs 8.2; p < 0.001) and VAS scores (4.5 vs 1.3; p < 0.001), were seen with facet distraction of 3 mm or more. Patients who went on to have a posterior fusion also had increased NDI and VAS scores, independent of facet distraction. Conclusion: After undergoing ACDF for the treatment of cervical spine injury, patients with facet joint distraction of 3 mm or more have worse NDI and VAS pain scores. Cite this article: Bone Joint J 2018;100-B:1201-7.

The views and experiences of Malaysian primary care doctors in managing patients with chronic low back pain: a qualitative study.

BACKGROUND: Chronic low back pain (CLBP) is a common and often difficult to treat condition in the primary care setting. Research involving in-depth exploration on the views and experiences faced by primary care doctors in managing patients with CLBP in Malaysia is limited. OBJECTIVE: To explore the primary care practitioners' views and experiences in managing patients with CLBP. STUDY DESIGN: A qualitative approach was employed using focus group discussions (FGD) at an academic primary care clinic in Kuala Lumpur, Malaysia. Twenty-three primary care doctors were purposively selected. Data were collected through audio-recorded interviews, which were transcribed verbatim and checked for accuracy. Data saturation was reached by the third FGD. An additional FGD was included to ensure completeness. A thematic approach using the one sheet of paper (OSOP) method was used to analyse the data. RESULTS: Participants view managing patients with CLBP as challenging. This is mainly due to the difficulty in balancing the doctors' expectations with the patients' perceived expectations during consultation. Barriers identified include lack of awareness and conflicting views regarding the usefulness of the local clinical practice guideline (CPG) in clinical practice. Other barriers include time constraints and perceived lack of support from multidisciplinary teams in managing these patients. CONCLUSION: Managing patients with CLBP is still a challenge for Malaysian primary care doctors. Any intervention should target identified barriers to improve the management of patients with CLBP.

Examination of the ovotoxicity of 5-fluorouracil in mice.

PURPOSE: Undesirable side effects of cancer treatments are common and include damage to the ovary, and depletion of the follicle reserve, which if severe enough, can lead to infertility and early menopause. Antimetabolite drugs, such as 5-fluorouracil (5-FU), are not considered to be detrimental to the ovary, but the ovotoxicity of 5-FU has not been evaluated in any detail. The purpose of this study was to evaluate the effects of 5-FU on follicle number. METHODS: In this study, adult female C57Bl6 mice (n = 4-6 animals/group) received a single dose of saline or 5-FU (150 mg/kg) and markers of ovarian damage and follicle depletion were assessed 12 h and 7 days later. RESULTS: Exposure to 5-FU did not alter primordial and primary follicle numbers. Atresia of secondary and antral follicles was increased significantly 12 h after 5-FU treatment, but atresia rates returned to levels similar to that of saline treated controls at 7 days. The number of corpora lutea were reduced 7 days after exposure to 5-FU, possibly as a consequence of earlier follicular atresia. CONCLUSIONS: These findings suggest that a single dose of 5-FU is mildly ovotoxic, but any effects on ovarian function are likely transient because the primordial follicle population is not depleted. Collectively, these data support the notion that 5-FU is unlikely to impact on the long-term fertility of women.