Experimental infection of tick cells with Nipah virus.

Nipah virus (NiV), a highly pathogenic henipavirus of the family Paramyxoviridae, which causes fatal encephalitis in 40-70% of affected patients, was first reported in Malaysia over 20 years ago. Pteropid bats are the natural hosts of henipaviruses, and ticks have been proposed as a possible link between bats and mammalian hosts. To investigate this hypothesis, infection of the tick cell line IDE8 with NiV was examined. Presence of viral RNA and antigen in the NiV-infected tick cells was confirmed. Infectious virions were recovered from NiV-infected tick cells and ultrastructural features of NiV were observed by electron microscopy. These results suggest that ticks could support NiV infection, potentially playing a role in transmission.

[Correlation between fluid parameter and cardiovascular events in hemodialysis patients based on repeated body composition analyses].

Objective: To explore the correlation between fluid load index and cardiovascular events in hemodialysis patients based on repeated body composition analyses. Methods: A prospective cohort study was conducted to collect the clinical data of patients undergoing maintenance hemodialysis (MHD) in the Department of Nephrology, Hangzhou Hospital of Traditional Chinese Medicine from July to September 2020. The pre-dialysis fluid overload (FO) index-overhydration (OH) was measured by bioelectrical impedance method, and the follow-up monitoring was conducted every 6 months. According to the baseline OH value, patients were divided into non-FO group (OH≤2.5 L) and FO group (OH>2.5 L). Moreover, according to the repeated measurements, the patients were divided into continuous non-FO group, continuous FO group and intermittent FO group. All patients were followed up until October 1, 2022, and the outcomes were recorded. The end point of follow-up was cardiovascular events. The cumulative incidence of cardiovascular events was calculated by the Kaplan-Meier method, and the risk factors of cardiovascular events were analyzed by Cox proportional hazards regression model. Results: A total of 289 patients were included, including 88 patients (30.4%) with FO and 201 patients (69.6%) with non-FO. There were 168 males (58.1%) and 121 (41.9%) females, with an average age of (58±13) years and an average follow-up time of (22.0±6.5) months. Kaplan-Meier analysis showed that the incidence of cardiovascular events in the baseline FO group was higher than that in the non-FO group (log-rank χ2=14.44, P<0.001). The incidence of cardiovascular events in both the continuous FO group and the intermittent FO group was higher than that in the continuous non-FO group (log-rank χ2=41.47, P<0.001; log-rank χ2=18.36, P<0.001). After adjustment for gender, age, comorbidities, and biochemical indicators, the incidence of cardiovascular events in the baseline FO group was 1.850 times of the non-FO group (95%CI: 1.046-3.271, P=0.034). The incidence of cardiovascular events in the continuous FO group was 4.679 times of the continuous non-FO group (95%CI: 2.189-10.002, P<0.001). The incidence of cardiovascular events in the intermittent FO group was 3.410 times of the continuous non-FO group (95%CI: 1.696-6.857, P=0.001). Conclusions: OH value measured by bioelectrical impedance can be used as an important reference index for clinical monitoring of cardiovascular events in MHD patients. Continuous chronic and intermittent exposures to FO are risk factors for cardiovascular events in hemodialysis patients.

Experimental infection of tick cells with Nipah virus

@#Nipah virus (NiV), a highly pathogenic henipavirus of the family Paramyxoviridae, which causes fatal encephalitis in 40-70% of affected patients, was first reported in Malaysia over 20 years ago. Pteropid bats are the natural hosts of henipaviruses, and ticks have been proposed as a possible link between bats and mammalian hosts. To investigate this hypothesis, infection of the tick cell line IDE8 with NiV was examined. Presence of viral RNA and antigen in the NiV-infected tick cells was confirmed. Infectious virions were recovered from NiV-infected tick cells and ultrastructural features of NiV were observed by electron microscopy. These results suggest that ticks could support NiV infection, potentially playing a role in transmission.

A conventional multiplex PCR for the detection of four common soil-transmitted nematodes in human feces: development and validation.

Soil-transmitted helminth (STH) infections, mainly caused by Ascaris lumbricoides, Trichuris trichiura, and hookworms, are among the most common intestinal parasites that infect humans. The infections are widely distributed throughout tropical and subtropical countries, including Malaysia, particularly in underprivileged communities. Microscopic and culture techniques have been used as a gold standard for diagnostic techniques. However, these methods yield low sensitivity and specificity, laborious and time-consuming. Therefore, simple, rapid, and accurate alternative methods are needed for the simultaneous detection of STH infections. Although advanced technologies such as real-time multiplex PCR have been established, the use of this technique as a routine diagnostic is limited due to the high cost of the instrument. Therefore, a single-round multiplex conventional PCR assay for rapid detection of four STH species in the fecal sample was developed in this study. To perform the single-round multiplex PCR, each pair of species-specific primers was selected from target genes, including Ancylostoma duodenale (Internal Transcribed Spacer 2; accession No. AJ001594; 156 base pair), Necator americanus (ITS 2; accession No. AJ001599; 225 base pair), Ascaris lumbricoides (Internal Transcribed Spacer 1; accession No. AJ000895; 334 base pair) and Trichuris triciura (partial ITS 1, 5.8s rRNA and partial ITS 2; accession No. AM992981; 518 base pair). The results showed that the newly designed primers could detect the DNA of STH at low concentrations (0.001 ng/ µl) with no cross-amplification with other species. This assay enables the differentiation of single infections as well as mixed infections. It could be used as an alternative and is a convenient method for the detection of STHs, especially for the differentiation of N. americanus and A. duodenale.

A conventional multiplex PCR for the detection of four common soil-transmitted nematodes in human feces: development and validation

@#Soil-transmitted helminth (STH) infections, mainly caused by Ascaris lumbricoides, Trichuris trichiura, and hookworms, are among the most common intestinal parasites that infect humans. The infections are widely distributed throughout tropical and subtropical countries, including Malaysia, particularly in underprivileged communities. Microscopic and culture techniques have been used as a gold standard for diagnostic techniques. However, these methods yield low sensitivity and specificity, laborious and time-consuming. Therefore, simple, rapid, and accurate alternative methods are needed for the simultaneous detection of STH infections. Although advanced technologies such as real-time multiplex PCR have been established, the use of this technique as a routine diagnostic is limited due to the high cost of the instrument. Therefore, a single-round multiplex conventional PCR assay for rapid detection of four STH species in the fecal sample was developed in this study. To perform the single-round multiplex PCR, each pair of species-specific primers was selected from target genes, including Ancylostoma duodenale (Internal Transcribed Spacer 2; accession No. AJ001594; 156 base pair), Necator americanus (ITS 2; accession No. AJ001599; 225 base pair), Ascaris lumbricoides (Internal Transcribed Spacer 1; accession No. AJ000895; 334 base pair) and Trichuris triciura (partial ITS 1, 5.8s rRNA and partial ITS 2; accession No. AM992981; 518 base pair). The results showed that the newly designed primers could detect the DNA of STH at low concentrations (0.001 ng/μl) with no cross-amplification with other species. This assay enables the differentiation of single infections as well as mixed infections. It could be used as an alternative and is a convenient method for the detection of STHs, especially for the differentiation of N. americanus and A. duodenale.

One-year outcomes of an osteoporosis liaison services program initiated within a healthcare system.

Due to the huge gap in the care of patients with osteoporosis and fragility fractures, we aimed to explore the effectiveness of the osteoporosis liaison service (OLS) in osteoporosis care. We found that OLS can improve osteoporosis care, including increasing medication compliance, increasing calcium/vitamin D/protein intake, and reducing fall rate. INTRODUCTION: A significant gap exists in the care of patients with osteoporosis and fragility fractures. This study aimed to evaluate 1-year outcomes of an osteoporosis liaison service (OLS) program that includes two independent components: medication management services (MMS) to improve medication adherence and fracture liaison services (FLS) for secondary prevention. METHODS: Patients with new hip fracture or untreated vertebral fractures enrolled in the FLS program (n = 600), and those with osteoporosis medication management issues but not necessarily fragility fractures enrolled in the MMS program (n = 499) were included. To evaluate outcomes, care coordinators assessed baseline items adapted from the 13 Best Practices Framework (BPF) standards of the International Osteoporosis Foundation, with telephone follow-up every 4 months for 1 year. RESULTS: Mean age of this cohort was 76.2 ± 10.3 years, 78.8% were female. After 1-year participation in the program, all patients had received bone mineral density tests, and medication adherence for the entire cohort at 12 months was 91.9 ± 19.6%, with significant improvement in fall rates (23.4% reduction), exercise rates (16.8% increase), calcium intake (26.5% increase), vitamin D intake (26.4% increase), and adequate protein intake (17.3% increase) (all p < 0.05). After 1-year OLS program, the overall rates of mortality, incident fracture, and falls were 6.6%, 4.0%, and 24.3%, respectively. CONCLUSIONS: The OLS program is associated with improved osteoporosis care, including increased medication adherence, calcium/vitamin D and protein intake, and reduced fall rate.

miR-34a and miR-125a-5p inhibit proliferation and metastasis but induce apoptosis in hepatocellular carcinoma cells via repressing the MACC1-mediated PI3K/AKT/mTOR pathway.

microRNA-34a (miR-34a) and microRNA-1251-5p (miR-125a-5p) were considered as tumor suppressors in hepatocellular carcinoma (HCC). Nevertheless, the modulatory mechanisms of miR-34a and miR-125a-5p in HCC haven't been completely understood. The levels of metastasis-associated with colon cancer 1 (MACC1) and miRNAs (miR-34a and miR-125a-5p) were determined by quantitative real-time polymerase chain reaction (qRT-PCR), and the levels of associated proteins were detected by western blot assay. Cell proliferation and metastasis were examined via Cell Counting Kit-8 (CCK-8) and transwell assays, respectively. Cell apoptosis was measured through flow cytometry. The effect of MACC1 on HCC in vivo was explored via xenograft assay. Dual-luciferase reporter assay and RNA Immunoprecipitation (RIP) assay were implemented to explore the target correlation. The expression of MACC1 was upregulated in HCC tissues and cells. Knockdown of MACC1 inhibited proliferation and metastasis but expedited apoptosis of HCC cells and the repression of tumor growth in vivo was evoked by MACC1 downregulation. Both miR-34a and miR-125a-5p directly targeted MACC1 and repressed the expression of MACC1 in HCC cells. Overexpression of miR-34a or miR-125a-5p restrained cell proliferation and metastasis while induced apoptosis by downregulating MACC1 in HCC cells. miR-34a and miR-125a-5p repressed phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signal pathway via reducing MACC1 in HCC cells. miR-34a and miR-125a-5p refrained proliferation and metastasis while motivated apoptosis in HCC cells through the PI3K/AKT/mTOR pathway by repressing MACC1. miR-34a and miR-125a-5p might be splendid biomarkers in the therapeutic strategies for HCC.

Toxoplasma gondii infection among selected indigenous community in Sarawak, East Malaysia.

Toxoplasma gondii is an obligate intracellular protozoan parasite that causes toxoplasmosis in humans. To date, little is known about T. gondii infection among the indigenous community, particularly in East Malaysia. This study was conducted to determine the status of T. gondii infection and to investigate associated risk factors among the indigenous community of Sarawak, East Malaysia. The sociodemographic data was obtained using a pretested questionnaire. A serological test was done to detect the presence of specific IgM and IgG antibodies against T. gondii in serum samples. A nested polymerase chain reaction (PCR) was used to determine acute infection among seropositive individuals. The overall seroprevalence of T. gondii infection was 50% (95% CI = 43.3 - 56.7). From this subset, 40.1%, 5.7%, and 4.2% were positive for anti-T. Gondii IgG antibodies, IgM, and both IgG and IgM, respectively. Four seropositive samples were amplified through PCR. None of the pregnant women tested positive for T. gondii infection based on the serological and PCR assays. A significant association was found between age, low monthly household income, unemployment, usage of untreated water and close contact with T. gondii seropositive cats. These results provide basic information on T. gondii infection and may be useful for policymakers to initiate prevention and control programs, especially amongst pregnant women and women of childbearing age in the indigenous community.

Toxoplasma gondii infection among selected indigenous community in Sarawak, East Malaysia

@#Toxoplasma gondii is an obligate intracellular protozoan parasite that causes toxoplasmosis in humans. To date, little is known about T. gondii infection among the indigenous community, particularly in East Malaysia. This study was conducted to determine the status of T. gondii infection and to investigate associated risk factors among the indigenous community of Sarawak, East Malaysia. The sociodemographic data was obtained using a pretested questionnaire. A serological test was done to detect the presence of specific IgM and IgG antibodies against T. gondii in serum samples. A nested polymerase chain reaction (PCR) was used to determine acute infection among seropositive individuals. The overall seroprevalence of T. gondii infection was 50% (95% CI = 43.3 – 56.7). From this subset, 40.1%, 5.7%, and 4.2% were positive for anti-T. Gondii IgG antibodies, IgM, and both IgG and IgM, respectively. Four seropositive samples were amplified through PCR. None of the pregnant women tested positive for T. gondii infection based on the serological and PCR assays. A significant association was found between age, low monthly household income, unemployment, usage of untreated water and close contact with T. gondii seropositive cats. These results provide basic information on T. gondii infection and may be useful for policymakers to initiate prevention and control programs, especially amongst pregnant women and women of childbearing age in the indigenous community.

[Combined use of wide-detector and adaptive statistical iterative reconstruction-V technique in abdominal CT with low radiation dose].

Objective: To investigate the image quality and radiation dose with wide-detector(80 mm) and adaptive statistical iterative reconstruction-V (ASIR-V) technique at abdominal contrast enhanced CT scan. Methods: In the first phantom experiment part, the percentage of ASIR-V for half dose of combined wide detector with ASIR-V technique as compared with standard-detector (40 mm) technique was determined. The human experiment was performed based on the phantom study, 160 patients underwent contrast-enhanced abdominal CT scan were prospectively collected and divided into the control group (n=40) with image reconstruction using 40% ASIR (group A) and the study group (n=120) with random number table. According to pre-ASIR-V percentage, the study group was assigned into three groups[40 cases in each group, group B: 0 pre-ASIR-V scan with image reconstruction of 0-100% post-ASIR-V (interval 10%, subgroups B0-B10); group C: 20% pre-ASIR-V with 20%, 40% and 60% post-ASIR-V (subgroups C1-C3); group D: 40%pre-ASIR-V with 40% and 60% post-ASIR-V (subgroups D1-D2)]. Image noise, CT attenuation values and CNR of the liver, pancreas, aorta and portal vein were compared by using two sample t test and One-way ANOVA. Qualitative visual parameters (overall image quality as graded on a 5-point scale) was compared by Mann-Whitney U test and Kruskal-Wallis H test. Results: The phantom experiment showed that the percentage of pre-ASIR-V for half dose was 40%. With the 40% pre-ASIR-V, radiation dose in the study group was reduced by 35.5% as compared with the control group. Image noise in the subgroups of B2-B10, C2-C3 and D1-D2 were lower (t=-14.681--3.046, all P<0.05) while CNR in the subgroups of B4-B10, C2-3 and D1-D2 were higher(t=2.048-9.248, all P<0.05)than those in group A, except the CNR of liver in the arterial phase (AP) in C2, D1 and D2 and the CNR of pancreas in AP in D1 (t=0.574-1.327, all P>0.05). The subjective image quality scores increased gradually in the range of 0-60% post-ASIR-V and decreased with post-ASIR-V larger than 70%. The overall image quality of subgroup B3-B8, C2-C3 and D1-D2 were higher than that in group A (Z=-2.229--6.533, all P<0.05). Conclusion: Compared with stand-detector together with ASIR technique, wide-detector combined with 40% pre-ASIR-V technique with 60% post-ASIR-V image reconstruction can reduce radiation dose while maintain good overall image quality.

Detection in Malaysia of a Borrelia sp. From Haemaphysalis hystricis (Ixodida: Ixodidae).

Spirochetes from the Borrelia genus are known to cause diseases in humans, namely Lyme disease and relapsing fever. These organisms are commonly transmitted to humans by arthropod vectors including ticks, mite, and lice. Here, we report the molecular detection of a Borrelia sp. from a Haemaphysalis hystricis Supino tick collected from wildlife in an Orang Asli settlement in Selangor, Malaysia. Phylogenetic analyses of partial 16s rRNA and flaB gene sequences revealed that the Borrelia sp. is closely related to the relapsing fever group borreliae, Borrelia lonestari, Borrelia miyamotoi, and Borrelia theileri, as well as a number of uncharacterized Borrelia sp. from ticks in Portugal and Japan. To our knowledge, this is the first report of a Borrelia sp. detected in H. hystricis, and in Malaysia. The zoonotic potential of this Borrelia sp. merits further investigation.

Eco-friendly luminescent solar concentrators with low reabsorption losses and resistance to concentration quenching based on aqueous-solution-processed thiolate-gold nanoclusters.

Heavy-metal-containing quantum dots (QDs) with engineered electronic states have been served as luminophores in luminescent solar concentrators (LSCs) with impressive optical efficiency. Unfortunately, those QDs involve toxic elements and need to be synthesized in a hazardous solvent. Recently, biocompatible, eco-friendly gold nanoclusters (AuNCs), which can be directly synthesized in an aqueous solution, have gained much attention for promising applications in 'green photonics'. Here, we explored the solid-state photophysical properties of aqueous-solution-processed, glutathione-stabilized gold nanoclusters (GSH-AuNCs) with a ligand-to-metal charge-transfer (LMCT) state for developing 'green' LSCs. We found that such GSH-AuNCs exhibit a large Stokes shift with almost no spectral overlap between the optical absorption and PL emission due to the LMCT states, thus, suppressing reabsorption losses. Compared with GSH-AuNCs in solution, the photoluminescence quantum yields (PL-QYs) of the LSCs can be enhanced, accompanied with a lengthened PL lifetime owing to the suppression of non-radiative recombination rates. In addition, the LSCs do not suffer from severe concentration-induced PL quenching, which is a common weakness for conventional luminophores. As a result, a common trade-off between light-harvesting efficiency and solid-state PL-QYs can be bypassed due to nearly-zero spectral overlap integral between the optical absorption and PL emission. We expect that GSH-AuNCs hold great promise for serving as luminophores for 'green' LSCs by further enhancing solid-state PL-QYs.

Body mass index and depressive symptoms in adolescents in Taiwan: testing mediation effects of peer victimization and sleep problems.

BACKGROUND: Despite recognition of the link between body mass index (BMI) and depression in adolescence, the underlying mechanisms behind this association remain understudied. This study aims to examine three mediational pathways from BMI to depressive symptoms through peer victimization and sleep problems. Sex differences in the mediating effects were also explored. METHODS: Data came from 1893 adolescents participating in a multi-wave longitudinal study from grade 9 to 12 in northern Taiwan were analyzed. Measures included BMI in 2009, peer victimization in 2010, sleep problems in 2011, depressive symptoms in 2012 and other covariates (sex, age, parental education, family structure, family economic stress, stressful life events, pubertal development and previous scores of focal study variables). A series of multiple regression models were conducted to test mediation hypotheses. A bootstrapping approach was applied to obtain confidence intervals for determining the significance of indirect effects. RESULTS: The association between BMI and depressive symptoms was significantly mediated by peer victimization and sleep problems. Higher BMI predicted more peer victimization and sleep problems, each of which led to higher levels of depressive symptoms. Our results further showed that higher BMI was associated with more peer victimization, which led to greater sleep problems and in turn resulted in increased depressive symptoms. No sex differences was found for the indirect effects of BMI on depressive symptoms through either peer victimization or sleep problems. CONCLUSIONS: Peer victimization and sleep problems partly explain the link between BMI and depressive symptoms. Interventions to prevent or manage depressive symptoms may yield better results if they consider the effects of these two psychosocial factors rather than targeting BMI alone.

[CT findings of inflammatory myofibroblastic tumor of different pathological types].

Objective: To explore the computed tomography(CT) features of inflammatory myofibroblastic tumor(IMT) in different pathological types, and improve the diagnostic level of this disease. Methods: The CT features of 29 cases pathologically confirmed IMTs were retrospectively reviewed along with a literature review to analyze the CT features and pathological correlations, and three kinds of pathological classification of IMT in patients with gender , shape, boundary and location were respectively analyzed by Chi-Square test. Results: The age ranges from 2 to 78 years.There were 7 cases of mucinous blood vessel type and 13 cases of spindle cell type and 9 cases of fiber type.Immunohistochemically, Vimentin (22/29) and SMA (28/29) were positive in all the cases, ALK (4/29) and CD-67(6/29) were partly positive expression, other markers such as S-100 were negative expression.The Chi-Square test showed that there were statistically differences in the gender of the patients. Conclusion: The CT and clinical features differ according to pathological types of IMT. Its final diagnosis still needs to be combined with pathology and immunohistochemistry result. In all, CT has a role in assessing the extension of IMT and especially about the relationship with adjacent organs which can effectively direct the establishment of clinical treating scheme.

Hepatitis C viraemia reversibly maintains subset of antigen-specific T-bet+ tissue-like memory B cells.

BACKGROUND: Chronic antigen exposure and/or ageing increases the frequency of T-box expressed in T cells (T-bet)-expressing B-lymphocytes in mice. The frequency and significance of B-cell T-bet expression during chronic hepatitis C (HCV) infection in human subjects has never been described. METHODS: Healthy controls, cirrhotic and noncirrhotic HCV-infected patients, and non-HCV patients with cirrhosis were recruited. Peripheral blood mononuclear cells were phenotyped for expression of T-bet and related markers by flow cytometry. In a subset of patients who underwent antiviral therapy and were cured of HCV infection (sustained virological response), the dynamics of T-bet expression in B cells was monitored. After cure, convalescent B cells were tested for T-bet expression after re-exposure to infected plasma or recombinant HCV proteins. RESULTS: Forty-nine patients including 11 healthy donors, 30 hepatitis C-infected individuals (nine with liver cancer, 13 with cirrhosis, eight without cirrhosis) and eight patients with cirrhosis due to non-HCV-related cause were recruited. We found that B cells in patients with chronic HCV exhibited increased frequency of T-bet+ B cells relative to noninfected individuals (median 11.5% v. 2.2%, P<.0001) but that there were no significant differences between noncirrhotic, cirrhotic and cancer-bearing infected individuals. T-Bet+ B cells expressed higher levels of CD95, CXCR3, CD11c, CD267 and FcRL5 compared to T-bet- B cells and predominantly exhibit a tissue-like memory CD27- CD21- phenotype independent of HCV infection. T-bet+ B cells in HCV-infected patients were more frequently class-switched IgD- IgG+ (40.4% vs. 26.4%, P=.012). Resolution of HCV infection with direct-acting antiviral (DAA) therapy leads to a marked reduction in the frequency of T-bet+ B cells (median 14.1% pretreatment v. 6.7% end of treatment v. 6.1% SVR12, P≤.01). Re-exposure of convalescent (cured) B cells to viremic plasma and recombinant HCV E2 protein led to re-expression of T-bet. CONCLUSION: Chronic antigenemia in chronic HCV infection induces and maintains an antigen-specific T-bet+ B cell. These B cells share markers with tissue-like memory B cells. Antigen-driven T-bet expression may be a critical suppressor of B-cell activation in chronic HCV infection.

Prolonged postprocedural outbreak of Mycobacterium massiliense infections associated with ultrasound transmission gel.

Postprocedural infections by Mycobacterium abscessus complex are increasing worldwide, and the source and route of transmission are infrequently identified. Here the extension of a previous clustering of paediatric patients with surgical site infections due to a single strain of the subspecies M. massiliense is reported. The investigation was conducted at a 2200-bed teaching hospital in Taiwan and included microbial surveillance of the environment (water, air, equipment and supplies) and a case-control study. We performed molecular identification and typing of the isolates by a trilocus sequencing scheme, confirmed by multilocus sequencing typing and pulsed-field gel electrophoresis. We investigated 40 patients who developed postprocedure soft tissue or bloodstream infections by M. massiliense (TPE101) during a 3-year period. Thirty-eight patients were identified at hospital A, and one newborn and her mother were identified at hospital B (185 km from hospital A). A case-control study identified the association of invasive procedures (adjusted odds ratio, 9.13) and ultrasonography (adjusted odds ratio, 2.97) (both p <0.05) with acquiring the outbreak strain. Isolates from the cases and unopened bottles of ultrasound transmission gel were all of strain ST48 and indistinguishable or closely related by pulsed-field gel electrophoresis. After replacement of contaminated gel, no new cases were detected during 18 months' follow-up. This investigation identified the use of contaminated gel as the common source causing an outbreak on a larger scale than had been recognized. Our findings halted production by the manufacturer and prompted revision of hospital guidelines.

MEK inhibitors: a new class of chemotherapeutic agents with ocular toxicity.

A new class of chemotherapeutic agents, MEK inhibitors, has recently been developed and is proving to be an effective treatment for a number of cancers. A pattern of ocular adverse events has followed these drugs through clinical trials and their association with retinopathy is only just beginning to be recognized. We present two cases of MEK inhibitor-associated retinopathy followed by a review of the current literature on ocular toxicity associated with MEK inhibitors. Patients undergoing treatment with MEK inhibitors appear to have high rates of multifocal serous retinal detachments as well as retinal vein occlusions. We present the first report of cystoid macular edema associated with MEK inhibitor use. The mechanism of these adverse events is still unclear though they seem to be related to oxidative stress and blood retinal barrier breakdown. Management of the ocular toxicity can range from observation to topical treatments or intravitreal injections. Fortunately most ocular adverse events appear to be self-limited and do not require discontinuing the MEK inhibitor. Discontinuation or decreased dosing of MEK inhibitors may be reserved for cases of severe sight-threatening ocular toxicity.

First report on the seroprevalence of the Crimean-Congo haemorrhagic fever virus, a tick-borne virus, in Malaysia's Orang Asli population.

OBJECTIVE: The Crimean-Congo haemorrhagic fever virus (CCHFV), which is transmitted by the ticks of Hyalomma spp. in general and H. marginatumin particular, can cause severe disease in humans, with mortality rates of 3-30%. Other than from the bites of infected ticks, CCHFV can also be transmitted through contact with patients with the acute phase of infection or contact with blood or tissues from viraemic livestock.  Outbreaks of human cases of haemorrhagic manifestations have been documented since 1945 and described in parts of Africa, Asia, Eastern Europe and the Middle East and most recently India in 2011. In addition, serological evidence of the disease has been reported in some countries where no human cases were reported. As regional neighbours China and India have been affected by this virus, this study was conducted to determine the seroprevalence of CCHFV among Orang Asli population of Malaysia as the most at risk people who residing in the deep forests. PATIENTS AND METHODS: A total of 682 serum samples were collected from the Orang Asli population residing in eight states in peninsular Malaysia and analysed for the presence of anti-CCHFV immunoglobulin G (IgG) using a commercial enzyme-linked immunosorbent assay kit. RESULTS: The study subjects comprised 277 (40.6%) men and 405 (59.4%) women. However, anti-CCHFV IgG was detected in only one female serum sample (0.1%). The presence of anti-CCHFV IgG could not be correlated to age or sex from these findings. CONCLUSIONS: The results of this screening survey showed that the seroprevalence of the anti-CCHFV IgG among Malaysia's Orang Asli population is too low for detection or totally negative compared with that in neighbouring countries, such as India and China.

Modeling tenderness for genetic and quantitative trait loci analyses.

Tenderness is the one of the most important attributes of beef with regards to the intent of consumers to repurchase. Beef tenderness is frequently measured objectively as Warner-Bratzler shear force. However, to better understand the genetics underlying tenderness, better descriptors were derived herein. Two traits, adjusted shear force and aging rate, were calculated to incorporate measures of Warner-Bratzler shear force repeated over aging time of 2 muscles, longissimus dorsi (LD) and semitendinosus (ST). Analysis of these traits indicated that the shear forces of the 2 muscles are lowly correlated and aging rate, as calculated, was not correlated with adjusted shear force. Breed, SNP, and QTL effects were analyzed for the 4 traits (2 traits × 2 muscles). For adjusted shear force, the QTL were located on cattle chromosomes BTA 5, 18, 25, and 29. With the exception of the QTL on BTA 5, the adjusted shear force QTL were observed for either the LD or the ST but not both muscles. The QTL for aging rate were located on BTA 1, 4, 7, 11, 13, 19, and 20.