Dissecting the Biology of Rafflesia Species: Current Progress and Future Directions Made Possible with High-Throughput Sequencing Data.

The angiosperm Rafflesia exhibits a unique biology, including a growth strategy that involves endophytic parasitism of a specific host, with only the gigantic flower externally visible. The Rafflesia possesses many unique evolutionary, developmental and morphological features that are rooted in yet-to-be-explained physiological processes. Although studies on the molecular biology of Rafflesia are limited by sampling difficulties due to its rarity in the wild and the short life span of its flower, current advances in high-throughput sequencing technology have allowed for the genome- and transcriptome-level dissection of the molecular mechanisms behind the unique characteristics of this parasitic plant. In this review, we summarize major findings on the cryptic biology of Rafflesia and provide insights into future research directions. The wealth of data obtained can improve our understanding of Rafflesia species and contribute toward the conservation strategy of this endangered plant.

Clinical and laboratory observation on immunoglobulin replacement therapy switching from an intravenous to a subcutaneous route in a Malaysian X-linked agammaglobulinemia patient.

We report a clinical and laboratory observation in a boy with X-linked agammaglobulinemia (XLA) who underwent an immunoglobulin replacement therapy (IRT) via the subcutaneous route (IGSC) seven years after his IRT via intravenous route (IGIV). He was free of invasive infections when on IGIV but not the troublesome coughs a week before the next infusion. A switch to a subcutaneous route resulted in significant improvement of symptoms with good weight gain. When on 2-weekly IGSC cycle, adjusting dose for weight resulted in an IgG trough level of > 600 mg/dl.

Titanium dioxide fiber saturable absorber for Q-switched fiber laser generation in the 1-micrometer region: publisher's note.

This publisher's note serves to correct an error in Appl. Opt. 58, 3495 (2019)APOPAI0003-693510.1364/AO.58.003495.

Titanium dioxide fiber saturable absorber for Q-switched fiber laser generation in the 1-micrometer region.

A passively Q-switched ytterbium-doped fiber laser (YDFL) operating at 1062 nm was demonstrated by using a segment of 20 cm titanium dioxide-doped fiber saturable absorber (TiO2DF SA). The Q-switched YDFL emerged stably with tunable repetition rates ranging from 32 kHz to 53 kHz as the pump power rose from 109 mW to 233 mW. Within this range of pump power, a maximum output power of 10.1 mW, maximum peak power of 75 mW, and maximum pulse energy of 191 nJ were obtained. The narrowest pulse width of 2.55 µs was attained at the maximum pump power of 233 mW, while the signal-to-noise ratio of the fundamental frequency was 47 dB. This demonstration reveals that the proposed TiO2DF SA is feasible for constructing a flexible and reliably stable Q-switched pulsed fiber laser in the 1-micrometer region.

The EAACI/GA²LEN/EDF/WAO guideline for the definition, classification, diagnosis and management of urticaria.

This evidence- and consensus-based guideline was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. The conference was held on 1 December 2016. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the EU-founded network of excellence, the Global Allergy and Asthma European Network (GA²LEN), the European Dermatology Forum (EDF) and the World Allergy Organization (WAO) with the participation of 48 delegates of 42 national and international societies. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease, presenting with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria are disabling, impair quality of life and affect performance at work and school. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomechanisms. In addition, it outlines evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.

Mode-locking pulse generation with MoS2-PVA saturable absorber in both anomalous and ultra-long normal dispersion regimes.

We experimentally demonstrate a stable and simple mode locked erbium doped fiber laser (EDFL) utilizing passive few-layer molybdenum disulfide (MoS2) as a saturable absorber. The MoS2 is obtained by liquid phase exfoliation before it is embedded in a polymer composite film and then inserted in the laser cavity. A stable soliton pulse train started at a low threshold pump power of 20 mW in the anomalous dispersion regime after fine-tuning the rotation of the polarization controller. The central wavelength, 3 dB bandwidth, pulse width, and repetition rate of the soliton pulses are 1574.6 nm, 9.5 nm, 790 fs, and 29.5 MHz, respectively. By inserting a 850 m long dispersion shifted fiber (DSF) in the cavity, a dissipative soliton with square pulse train is obtained in the normal dispersion regime where the operating wavelength is centered at 1567.44 nm with a 3 dB bandwidth of 19.68 nm. The dissipative soliton pulse has a pulse width of 90 ns at a low repetition rate of 231.5 kHz due to the long DSF used. These results are a contribution to the pool of knowledge in nonlinear optical properties of two-dimensional nanomaterials especially for ultrafast photonic applications.

Momordica charantia ointment accelerates diabetic wound healing and enhances transforming growth factor-ß expression.

OBJECTIVE: Transforming growth factor-ß (TGF-ß) plays an important role in wound healing. Delayed wound healing is a consequence of diabetes, leading to high morbidity and poor quality of life. Momordica charantia (MC) fruit possesses anti-diabetic and wound healing properties. This study aimed to explore the changes in TGF-ß expression in diabetic wounds treated with topical MC fruit extract. METHODS: Fifty-six male Sprague-Dawley rats were divided into a normal control group and five diabetic groups of ten rats each. Intravenous streptozotocin (50mg/kg) was given to induce diabetes in the diabetic groups. Full thickness excision wounds were created on the thoracodorsal region of the animals, and these wounds were then treated with vehicle, MC powder, MC ointment and povidone ointment or ointment base for ten days. Wound healing was determined by the rate of wound closure, total protein content and TGF-ß expression in the wounds, and histological observation. RESULTS: Diabetic groups showed delayed wound closure rates compared to the control group. The wound closure rate in the MC ointment group was significantly faster than that of the untreated diabetic group (p<0.05). The MC ointment group also showed intense TGF-ß expression and a high level of total protein content. CONCLUSION: MC ointment has a promising potential for use as an alternative topical medication for diabetic wounds. This work has shown that it accelerates wound healing in diabetic rats, and it is suggested here that this occurs by enhancing TGF-ß expression. Further work is recommended to explore this effect.

Parental reports of behavioural outcome among paediatric leukaemia survivors in Malaysia: a single institution experience.

OBJECTIVES: To determine the behavioural impact of chemotherapy in survivors of acute lymphoblastic leukaemia (ALL) treated with chemotherapy only and to identify treatment-related or sociodemography-related factors that might be associated with behavioural outcome. METHODS: We examined 57 survivors of childhood ALL, who were off treatment for at least 2 years and were in remission, aged 4-18 years, and 221 unrelated healthy controls. The Child Behaviour Checklist (CBCL) parent report was used either in English or in Bahasa Malaysia (the national language of Malaysia) to assess the behavioural outcome. RESULTS: Childhood ALL survivors had significantly higher scores on externalising behaviour on the CBCL parent report than did controls. Higher problem scores were found in ALL survivors with single parents on 'total problems' (P = 0.03) and subscales 'withdrawn' (P = 0.03), 'social problems' (P < 0.01) and 'delinquent behaviour' (P = 0.03) than in survivors with married parents. Significant associations were seen between a lower education level of the father and the variables representing internalising (withdrawn, anxious/depressed) and externalising (aggressive behaviour). We observed trends on higher scores in all scales in ALL survivors with single parents than in controls with single parents or with fathers with low education level, especially primary education only. CONCLUSIONS: Malaysian childhood ALL survivors had a significantly increased risk for externalising behavioural problems, and there was a trend towards increased risk of problems in many other behavioural scales. Understanding the sociocultural dimension of patients' health is important to be able to design the most appropriate remedy for problem behaviours detected in this multi-ethnic population.

Methods report on the development of the 2013 revision and update of the EAACI/GA2 LEN/EDF/WAO guideline for the definition, classification, diagnosis, and management of urticaria.

This methods report describes the process of guideline development in detail. It is the result of a systematic literature review using the 'Grading of Recommendations Assessment, Development and Evaluation' (GRADE) methodology and a structured consensus conference held on 28 and 29 November 2012, in Berlin. It is a joint initiative of the Dermatology Section of the European Academy of Allergy and Clinical Immunology (EAACI), the EU-funded network of excellence, the Global Allergy and Asthma European Network (GA(2) LEN), the European Dermatology Forum (EDF), and the World Allergy Organization (WAO) with the participation of delegates of 21 national and international societies. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomechanisms. In addition, it outlines evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS) and is published in Allergy 2014; 69:868-887.

The EAACI/GA(2) LEN/EDF/WAO Guideline for the definition, classification, diagnosis, and management of urticaria: the 2013 revision and update.

This guideline is the result of a systematic literature review using the 'Grading of Recommendations Assessment, Development and Evaluation' (GRADE) methodology and a structured consensus conference held on 28 and 29 November 2012, in Berlin. It is a joint initiative of the Dermatology Section of the European Academy of Allergy and Clinical Immunology (EAACI), the EU-funded network of excellence, the Global Allergy and Asthma European Network (GA(2) LEN), the European Dermatology Forum (EDF), and the World Allergy Organization (WAO) with the participation of delegates of 21 national and international societies. Urticaria is a frequent, mast cell-driven disease, presenting with wheals, angioedema, or both. The life-time prevalence for acute urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria do not only cause a decrease in quality of life, but also affect performance at work and school and, as such, are members of the group of severe allergic diseases. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomechanisms. In addition, it outlines evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS).

Clinical-Epidemiological Pattern of Primary Immunodeficiencies in Malaysia 1987-2006: A 20 year experience in Four Malaysian Hospitals.

AIM OF STUDY: To determine the clinical and epidemiological characteristics of patients seen with primary immunodeficiencies referred at four Malaysian Hospitals between 1987 to 2007. METHODS: Patient data were retrospectively obtained from patient records and supplemented by information from a standardized questionnaires taken at the time of diagnosis from 4 participating hospitals. The completed data were transferred to document records kept by the first author. The diagnoses made were based on criteria set by WHO Scientific Committee 1986. RESULTS: Fifty one (51) patients with completed records satisfied the criteria of primary immunodeficiencies based on WHO Scientific Committee 1986. Predominant Antibody deficiency (40.4%) is the commonest of the class of primary immunodeficiency (based on modified IUIS classification) followed by phagocytic defect (17.3%), combined immunodeficiencies (15.4%) and other cellular immunodeficiencies (11.5%). The commonest clinical presentation is pneumonia (54%) . A positive Family history with a close family relative afflicted was a strong pointer to diagnosis for PID (52.6%) Primary immnodeficiencies are seen in all the major ethnic groups of Malaysia, predominantly among Malays. As observed in other patient registries, diagnostic delay remains the major cause of morbidity and mortality. CONCLUSION: Primary immunodeficiencies is relative rare but is an emerging disease in Malaysia. Creating awareness of the disease, may reveal more cases within the community. It is sufficient to be a health issue in Malaysia as in other developing countries in the future.

Tocotrienol rich fraction (TRF) supplementation protects against oxidative DNA damage and improves cognitive functions in Wistar rats.

AIM: Oxidative stress is caused by imbalance between the productions of reactive oxygen species (ROS) and antioxidant defense mechanisms. Palm oil antioxidants such as tocotrienol rich fraction (TRF) is known to have neuroprotective effects on neurones by acting against free radical induced neuronal cell death. This study was undertaken to elucidate the effect of TRF on oxidative DNA damage and cognitive functions in experimental rats. MATERIALS AND METHODS: A total of 20 male Wistar rats (aged 3 months) were divided into 2 groups: (i) control group fed with distilled water and (ii) experimental group fed with TRF (200 mg/ kg body weight) for 8 months. DNA damage was determined using Comet assay. Antioxidant enzymes like superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) were assessed in the blood. The Morris Water Maze (MWM) test was used to evaluate the cognitive functions. RESULTS: DNA damage was significantly reduced in the experimental group supplemented with TRF compared to the control group (p <0.05). In the group supplemented with TRF, the percentage of DNA damage was 2.87 ± 0.48% compared to 5.96 ± 0.43% in the control group. SOD, GPx, and CAT enzyme activities increased in experimental group. Results from MWM showed improvement in cognitive functions as determined by latency to target platform, swim path and average speed between TRF and control groups. CONCLUSIONS: Continuous supplementation of TRF for 8 months reduced DNA damage and exhibited positive influence in spatial learning and memory.

Health-related quality of life (HRQOL) among pediatric leukemia patients in Malaysia.

BACKGROUND: Health-Related Quality of Life (HRQOL) in pediatric leukemia patients in Malaysia has not been studied before. This was mainly due to a lack of databases on patients in the past. Many patients abandoned treatment or were lost to follow up. With more children now fully compliant and completing treatment nowadays, with higher cure rate, HRQOL has become important for our patients. The purpose of the current study was to determine the HRQOL scores in children with acute leukemia and to compare the scores for those on maintenance chemotherapy with those off-treatment as well as to determine factors which might affect HRQOL. METHODS: Seventy-seven children in a pediatric oncology center in Kuala Lumpur, Malaysia diagnosed with acute leukemia were consecutively enrolled, of whom 22 were on maintenance chemotherapy and 55 off-treatment. The Pediatric Quality of Life Inventory (PedsQL™) Scales were used to assess HRQOL. RESULTS: Children on maintenance chemotherapy had significantly lower child self-report HRQOL scores across all domains (P < 0.001) especially psychosocial health compared with those who were off-treatment. Also, parents with children on maintenance chemotherapy reported significantly lower HRQOL scores across all domains (P < 0.05) except social functioning compared with parents with children off-treatment. Younger child age was associated with lower parent proxy-report total score (P = 0.007) CONCLUSIONS: Pediatric acute leukemia patients on maintenance chemotherapy experienced significantly poorer HRQOL compared to those off-treatment.

Atlanto-occipital fusion: an osteological study with clinical implications.

BACKGROUND: Atlanto-occipital fusion may be symptomatic or asymptomatic in nature. The anomaly may be incidentally detected at autopsies or during routine cadaveric dissections. The fusion of the atlas with occipital bone may result in the compression of vertebral artery and first cervical nerve. METHODS: A total of 55 dried occipital bones in the Department of Anatomy, Universiti Kebangsaan Malaysia (UKM) and Department of Anatomy, Universiti Malaya (UM) were included in the study. The presence of atlantooccipital fusion was closely observed and morphometric measurements were taken. RESULTS: Out of 55 dried occipital bones studied, we observed atlanto-occiptalization in two bones (3.63 %). A total of 53 occipital bones (96.37 %) did not exhibit any anomalous fusions. Out of the two anomalous atlanto-occiptal fusions, one was complete while the other had unilateral right-sided fusion of the atlas with the occipital bone. CONCLUSION: Atlanto-occipitalization may result in the compression of vertebral artery thereby influencing the blood flow to the brain. Atlanto-occipitalization may also result in compression of the first cervical nerve. The action of the postural muscles on the extensor surface may be affected as a result of this anomaly. The present article discusses the clinical implications of atlanto-occipitalization, which may be beneficial for neurosurgeons, neurologists and radiologists in day-to-day clinical practice (Fig. 3, Ref. 17).

The effect of Piper betel extract on the wound healing process in experimentally induced diabetic rats.

BACKGROUND: Piper betel (PB) possesses antimicrobial, antifungal, antioxidant and wound healing properties due to its powerful antioxidant effect. Diabetes mellitus (DM) is a metabolic disorder which is associated with complications like impaired wound healing, nephropathy and neuropathy. The main aim of the study was to study the wound healing properties of PB. MATERIALS AND METHODS: A total of 33 male Sprague-Dawley rats (250-300 g) were taken and divided into 3 groups: Group I (control) comprising of 14 rats; Group II (diabetic untreated) comprising of 9 rats; Group III (diabetic treated) comprising of 10 rats. After 10 days of acclimatization, the animals were fasted overnight and diabetes was induced by administration of streptozotocin (45 mg/Kg body weight in a single dose, through tail vein) to group II and III animals. Four 6 mm-diameter full thickness skin excision wounds were created and PB extract (50 mg diluted in 0.1 ml of normal saline) was applied locally for 10 days in group III. The group I and II received normal saline (0.1 ml) for 10 days. The total protein content and the wound contraction rate were determined. RESULTS: The wound contraction rate of group III (35.03 +/- 2.96) was higher as compared to group II (18.40 +/- 3.87) with p = 0.014. The total protein content for group III was 106.39 +/- 4.46 as compared to group II (72.86 +/- 12.86) with p = 0.050. CONCLUSION: PB acted as a protective agent in the early phase of wound healing by increasing total protein content and wound contraction rate.

The axillary arch - morphological and histological study with clinical importance.

The latissimus dorsi is a muscle of the back which forms the posterior fold of the axilla and its tendon twists to insert into the floor of the intertubercular sulcus of the humerus. Occasionally, the muscle has a muscular slip which crosses the axilla to insert into the pectoralis major. This muscular slip is often termed as "axillary arch." In the present study, we report bilateral axillary arch detected in a 45-year-old male cadaver. The average vertical length of the axillary arch measured 7 cm. The average maximum width of the uppermost, middle and lower part of the arch measured 2, 3.5 and 3.2 cm, respectively. The presence of the axillary arch is an uncommon finding in humans, considering the fact that it is solely found in the animals who prefer to hang on the trees. A histological study of the axillary arch was also performed and it showed skeletal muscle fibres which was uniformly arranged. The presence of the axillary arch may assist in the adduction of the shoulder. It may also compress the axillary vessels and nerves thereby causing resultant symptoms. Prior anatomical knowledge of the presence of axillary arch may be helpful for surgeons performing radical dissection of the axillary lymph nodes and ligation of axillary vessels, clinicians diagnosing abduction syndromes and interventional radiologists interpreting axillary mass in day to day clinical practice.

Two surgical methods used in 90 patients with intracranial subdural empyema.

We studied the efficacy of two surgical methods used for the treatment of intracranial subdural empyema (ISDE) at our centre. A cross-sectional study (1999-2005) of 90 patients with non-traumatic supratentorial ISDE revealed that the two surgical methods used for empyema removal were burr hole/s and drainage (50 patients, 55.6%) and a cranial bone opening procedure (CBOP) (40 patients, 44.4%). Patients in the CBOP group had a better result in terms of clinical improvement (chi-squared analysis, p=0.006) and clearance of empyema on brain CT scan (chi-squared analysis, p<0.001). Reoperation was more frequent among patients who had undergone burr hole surgery (multiple logistic regression, p<0.001). The outcome and morbidity of ISDE survivors were not related to the surgical method used (p>0.05). The only factor that significantly affected the morbidity of ISDE was level of consciousness at the time of surgery (multiple logistic regression, p<0.001). We conclude that CBOP and evacuation of the empyema is a better surgical method for ISDE than burr hole/s and drainage. Wide cranial opening and empyema evacuation improves neurological status, gives better clearance of the empyema and reduces the need for reoperation. Level of consciousness at the time of presentation is a predictor of the morbidity of ISDE. Thus, aggressive surgical treatment should occur as early as possible, before the patient deteriorates.

A histological study of the structural changes in the liver of streptozotocin-induced diabetic rats treated with or without Momordica charantia (bitter gourd).

AIM: Diabetic liver is associated with biochemical, physiological and pathological changes. The aim of the present study was to evaluate the histological changes following administration of Momordica charantia (MC) in the streptozotocin (STZ) induced diabetic rats. MATERIALS AND METHODS: Eighteen Sprague-Dawley rats (n=18) were taken for this study. The animals were divided into 3 groups:- non-diabetic (n=6), untreated diabetic (n=6) and diabetic treated with MC extract (n=6). Diabetes was induced in the experimental rats via intravenous injection of streptozotocin (45 mg/kg body weight). MC extract (50 mg/kg body weight) was administered orally to the treated diabetic rats 10 days following induction. The liver tissues were collected on the 10th day following treatment and the histological study was performed using different staining methods which included hematoxylin and eosin (H&E), Verhoeff's van Gieson (VvG) and periodic acid Schiff (PAS). RESULTS: The liver of the diabetic rats showed involvement of the hepatocytes with features of inflammation. The portal triad in the diabetic liver showed extensive involvement in terms of accumulation of mucopolysaccharide deposits. Liver damage in the diabetic animals showed features of healing with administration of the MC extract. CONCLUSIONS: The MC extract due to its antioxidant role may be helpful in reversing the changes in the liver in diabetes mellitus.

The accessory foramen ovale of the skull: an osteological study.

The sphenoid bone is known to have several foramina and the foramen ovale is one amongst them. The foramen ovale transmits the mandibular nerve, accessory meningeal artery, lesser petrosal nerve and the emissary veins. There have been past reports on the variations of the different foramina present in the skull but there are no reports on the variations of the skull foramina from any of the South-East Asian countries. The present study aims to highlight the presence of an accessory foramen ovale in the skull in Malaysian population. Both sides of fifteen adult skulls (n = 30) were taken for observation of any variations in the foramen ovale. We observed the presence of accessory foramen ovale on the left side of a single skull (3.33%). The minute accessory foramen ovale was located 0.1 cm medial to the normal foramen ovale. The anomalous accessory foramen ovale was circular in shape and measured 0.1 cm in diameter. Anatomical knowledge of the foramen ovale is important for all neurosurgical procedures involving the trigeminal nerve and administration of anaesthesia in the mandibular nerve. Interestingly, the percutaneous biopsy of the cavernous sinus is also performed through the foramen ovale. Prior knowledge of the presence of an accessory foramen ovale may be important for academic, anthropological, forensic and clinical purpose and the present study aims to highlight such.

The effect of topical extract of Momordica charantia (bitter gourd) on wound healing in nondiabetic rats and in rats with diabetes induced by streptozotocin.

BACKGROUND: Momordica charantia (MC; bitter gourd) is a traditional herb commonly used for its antidiabetic, antioxidant, contraceptive and antibacterial properties. It is also used for the rapid healing of wounds. AIM: To observe the topical effect of MC extract on the wound-healing process in rats with diabetes induced by streptozotocin. METHODS: In total, 72 Sprague-Dawley rats were used for the study. The animals were subdivided into two groups: a nondiabetic group (n = 36) and a group with diabetes induced by streptozotocin (n = 36). Both groups were subdivided further into a nontreated control group (n = 18), and a topically treated group with MC extract administered daily (n = 18). The wound was inflicted with a 6-mm punch-biopsy needle on the dorsal aspect of the thoracolumbar region. The animals were killed on the days 1, 5 and 10 after wound creation. The rate of wound closure and the total protein content was estimated. Histological study of the wound tissue at days 5 and 10 was also performed. RESULTS: The diabetic group exhibited delayed wound healing as compared to the normal group. Interestingly, the diabetic group treated with topical MC extract showed better results than the nontreated group. CONCLUSION: Results show that administration of MC extract improves and accelerates the process of wound healing in diabetic animals.