Plasmodium knowlesi circumsporozoite protein: genetic characterisation and predicted antigenicity of the central repeat region.

Circumsporozoite protein (CSP) central repeat region is one of the main target regions of the RTS,S/AS01 vaccine for falciparum infection as it consists of immunodominant B cell epitopes. However, there is a lack of study for P. knowlesi CSP central repeat region. This study aims to characterise the CSP repeat motifs of P. knowlesi isolates in Peninsular Malaysia. CSP repeat motifs of 64 P. knowlesi isolates were identified using Rapid Automatic Detection and Alignment of Repeats (RADAR). Antigenicity of the repeat motifs and linear B cell epitopes were predicted using VaxiJen 2.0, BepiPred-2.0 and BCPred, respectively. A total of 35 dominant repeat motifs were identified. The repeat motif "AGQPQAQGDGANAGQPQAQGDGAN" has the highest repeat frequency (n=15) and antigenicity index of 1.7986. All the repeat regions were predicted as B cell epitopes. In silico approaches revealed that all repeat motifs were antigenic and consisted of B cell epitopes which could be designed as knowlesi malaria vaccine.

Plasmodium knowlesi circumsporozoite protein: genetic characterisation and predicted antigenicity of the central repeat region

@#Circumsporozoite protein (CSP) central repeat region is one of the main target regions of the RTS,S/AS01 vaccine for falciparum infection as it consists of immunodominant B cell epitopes. However, there is a lack of study for P. knowlesi CSP central repeat region. This study aims to characterise the CSP repeat motifs of P. knowlesi isolates in Peninsular Malaysia. CSP repeat motifs of 64 P. knowlesi isolates were identified using Rapid Automatic Detection and Alignment of Repeats (RADAR). Antigenicity of the repeat motifs and linear B cell epitopes were predicted using VaxiJen 2.0, BepiPred-2.0 and BCPred, respectively. A total of 35 dominant repeat motifs were identified. The repeat motif “AGQPQAQGDGANAGQPQAQGDGAN” has the highest repeat frequency (n=15) and antigenicity index of 1.7986. All the repeat regions were predicted as B cell epitopes. In silico approaches revealed that all repeat motifs were antigenic and consisted of B cell epitopes which could be designed as knowlesi malaria vaccine.

Cloning, expression and purification of Plasmodium knowlesi circumsporozoite protein and immunoblot analysis with P. knowlesi strain A1H1 protein extract.

Circumsporozoite protein (CSP) is a sporozoite major surface protein of Plasmodium species. The protein showed promising protection level as a vaccine candidate against Plasmodium falciparum infection. There is a lack of studies on P. knowlesi CSP (PkCSP) as a vaccine candidate due to the high polymorphic characteristic of central repeat region. Recent studies showed the protein has a relatively conserved region at the C-terminal, which consists of T- and B-cell epitopes. This could be the target region for vaccine development against the pre-erythrocytic stage of the parasite. In this study, recombinant PkCSP was expressed using Escherichia coli system. Recombinant PkCSP was immunized in animal models and the antiserum was evaluated using immunoblot analysis. Results showed that PkCSP can be successfully expressed using the bacterial system. Endpoint titre of the antiserum were ranged up to 1:819200. Immunoblot analysis showed the antiserum recognized recombinant PkCSP but not total protein extract from P. knowlesi erythrocytic stage. In conclusion, PkCSP could elicit strong immune response in animal models. However, serum antibodies could not recognize protein from the parasite's erythrocytic stage extract indicating it is not expressed at the erythrocytic stage. Therefore, PkCSP remains as a potential pre-erythrocytic vaccine candidate against P. knowlesi infection.

The curious case of missing heartbeats.

Paroxysmal atrioventricular block (AVB) is a poorly defined and easily missed bradyarrhythmia, which can potentially lead to sudden cardiac death. It is under-recognised due to its abrupt onset and unpredictability. We describe a case that had paroxysmal AVB post-coronary angioplasty and highlight the mechanism as well as the management of this rare condition.

The Painful Anterior Apprehension Test - an Indication of Occult Shoulder Instability.

Introduction: To evaluate the clinical relevance of the painful anterior apprehension test in shoulder instability. Materials and methods: We performed a retrospective study of 155 patients that underwent arthroscopic anterior Bankart repair between 2014-2016. Exclusion criteria were previous ipsilateral shoulder surgery, bony Bankart lesions, glenohumeral osteoarthritis and concomitant surgery involving rotator cuff tears, biceps tendon pathology and superior labrum from anterior to posterior (SLAP) lesions. The study cohort was divided into three groups: apprehension test with apprehension only, apprehension test with pain only, and apprehension test with both apprehension and pain. Patient demographics, clinical characteristics, radiological imaging, arthroscopy findings and surgical outcomes (Constant, American Shoulder and Elbow Surgeons (ASES), SF-36 scores) were evaluated. Results: A total of 115 (74.2%) had apprehension only, 26 (16.8%) had pain only and 14 (9.0%) had pain and apprehension with the apprehension test. Univariate analysis showed significant differences between the groups in patients with traumatic shoulder dislocation (p=0.028), patients presenting with pain (p=0.014) and patients presenting with recurrent dislocations (p=0.046). Patients with a purely painful apprehension test were more likely to have a traumatic shoulder dislocation, more likely to present only with pain, and less likely to present with recurrent shoulder dislocations. Multivariate analysis showed that none of these factors alone were significant as single predictors for shoulder instability. All three groups were otherwise similar in patient profile, MRI and arthroscopic assessments, and clinical outcomes of surgery. Excellent clinical outcomes were achieved in all groups with no difference in pre-operative and post-operative scores across all groups at all time points. Conclusion: The painful apprehension test may suggest underlying shoulder instability.

The association between family dysfunction and admission to an acute mental health inpatient unit: a prospective study.

OBJECTIVES: With the shift from deinstitutionalization to community care in mental health services, relatives of persons with severe and enduring mental illnesses have had to take over the role as primary caregivers. Disturbed family dynamics have been observed within families with an 'ill' member. Although schizophrenia and related mental illnesses are biologically based disorders, environmental stress (including stress within family relationships) plays a major role in the onset and maintenance of symptoms. With this study, we assume that family dynamics play a central role in the course of severe psychiatric illness and hypothesized that dysfunction within family systems is a prognostic indicator of hospitalization in the course of schizophrenia/bipolar and schizoaffective disorders. METHODS: Prospective, observational cohort study evaluating family functioning of 121 patients (schizophrenia/bipolar and schizoaffective disorder) from community at baseline and followed-up over 12-month period after recruitment. Measurements included demographics, diagnosis, Family Assessment Device - General Functioning, Perceived Criticism Scale, Brief Psychiatric Rating Scale, Global Assessment of Functioning and Social Support Questionnaire-6. RESULTS: Significant differences found between patients admitted and not admitted during the 12-month time period for age (p = 0.003), Brief Psychiatric Rating Scale (BPRS; p = 0.026), Family Assessment Device - General Functioning (FAD-GF; p = 0.007) and Social Support Questionnaire total satisfaction level (p = 0.042) at baseline. Bivariate analysis showed that those admitted into hospital were younger with a higher BPRS score, less social satisfaction and disturbed family dynamics. FAD-GF (p = 0.006) and age (p = 0.022) were significant independent predictors for admission. CONCLUSION: This provides further evidence supporting importance of promoting better family functioning through modified family dynamics, integrating and involving family into the care of such patients.

Cloning, expression and purification of Plasmodium knowlesi circumsporozoite protein and immunoblot analysis with P. knowlesi strain A1H1 protein extract

@#Circumsporozoite protein (CSP) is a sporozoite major surface protein of Plasmodium species. The protein showed promising protection level as a vaccine candidate against Plasmodium falciparum infection. There is a lack of studies on P. knowlesi CSP (PkCSP) as a vaccine candidate due to the high polymorphic characteristic of central repeat region. Recent studies showed the protein has a relatively conserved region at the C-terminal, which consists of T- and B-cell epitopes. This could be the target region for vaccine development against the pre-erythrocytic stage of the parasite. In this study, recombinant PkCSP was expressed using Escherichia coli system. Recombinant PkCSP was immunized in animal models and the antiserum was evaluated using immunoblot analysis. Results showed that PkCSP can be successfully expressed using the bacterial system. Endpoint titre of the antiserum were ranged up to 1:819200. Immunoblot analysis showed the antiserum recognized recombinant PkCSP but not total protein extract from P. knowlesi erythrocytic stage. In conclusion, PkCSP could elicit strong immune response in animal models. However, serum antibodies could not recognize protein from the parasite’s erythrocytic stage extract indicating it is not expressed at the erythrocytic stage. Therefore, PkCSP remains as a potential pre-erythrocytic vaccine candidate against P. knowlesi infection.

Complications of Sub-microscopic Plasmodium vivax Malaria among Orang Asli in Pos Lenjang, Kuala Lipis.

In recent years, increasing cases of Plasmodium vivax complications had been reported all over the world. This former benign Plasmodium species is now recognized to be one of the human malaria parasites that can produce severe disease. In this article, we report two cases of sub-microscopic P. vivax malaria confirmed by PCR. Both patients were asymptomatic before treatment. They showed unusual presentations few days after initiation of antimalarial treatment. Both patients had subsequently completed antimalarial treatment and recovered completely.

Down-regulation of LINC00667 hinders renal tubular epithelial cell apoptosis and fibrosis through miR-34c

Purpose This study aimed to down-regulate LINC00667 and inhibit apoptosis and fibrosis of renal tubular epithelial cells through miR-34c. Methods Altogether, 98 patients with chronic kidney disease treated in our hospital were selected as the study group, and 67 normal people were selected as the control group. Epithelial cells of proximal convoluted tubules in human renal cortex were purchased. TGF-β1 was used to induce fibrosis of HK-2 renal tubular epithelial cells. The expression of LINC00667, miR-34c, type I collagen (Col 1) and type III collagen (Col 3) were detected by qRT-PCR and WB. Results LINC00667 was highly expressed in cancer tissues and HK-2, while miR-34c was poorly expressed. Inhibition of LINC00667 and over-expression of miR-34c could inhibit the proliferation and invasion of chronic kidney disease cells, but increase the apoptosis rate. Down-regulation of LINC00667 could significantly reduce of Col 1 and Col 3 in renal interstitial fibroblasts induced by TGF-β1, while up-regulation of miR-34c could also achieve this effect. Double luciferase report confirmed that there was a targeted regulatory relationship between LINC00667 and miR-34c. Conclusion LINC00667 could reduce the proliferation and invasion of chronic kidney disease cells, increase the apoptosis rate by regulating miR-34c, and improve renal fibrosis (AU)

Down-regulation of LINC00667 hinders renal tubular epithelial cell apoptosis and fibrosis through miR-34c.

PURPOSE: This study aimed to down-regulate LINC00667 and inhibit apoptosis and fibrosis of renal tubular epithelial cells through miR-34c. METHODS: Altogether, 98 patients with chronic kidney disease treated in our hospital were selected as the study group, and 67 normal people were selected as the control group. Epithelial cells of proximal convoluted tubules in human renal cortex were purchased. TGF-ß1 was used to induce fibrosis of HK-2 renal tubular epithelial cells. The expression of LINC00667, miR-34c, type I collagen (Col 1) and type III collagen (Col 3) were detected by qRT-PCR and WB. RESULTS: LINC00667 was highly expressed in cancer tissues and HK-2, while miR-34c was poorly expressed. Inhibition of LINC00667 and over-expression of miR-34c could inhibit the proliferation and invasion of chronic kidney disease cells, but increase the apoptosis rate. Down-regulation of LINC00667 could significantly reduce of Col 1 and Col 3 in renal interstitial fibroblasts induced by TGF-ß1, while up-regulation of miR-34c could also achieve this effect. Double luciferase report confirmed that there was a targeted regulatory relationship between LINC00667 and miR-34c. CONCLUSION: LINC00667 could reduce the proliferation and invasion of chronic kidney disease cells, increase the apoptosis rate by regulating miR-34c, and improve renal fibrosis.

Complications of Sub-microscopic Plasmodium vivax Malaria among Orang Asli in Pos Lenjang, Kuala Lipis

@#In recent years, increasing cases of Plasmodium vivax complications had been reported all over the world. This former benign Plasmodium species is now recognized to be one of the human malaria parasites that can produce severe disease. In this article, we report two cases of sub-microscopic P. vivax malaria confirmed by PCR. Both patients were asymptomatic before treatment. They showed unusual presentations few days after initiation of antimalarial treatment. Both patients had subsequently completed antimalarial treatment and recovered completely.

Wilms tumour with poor response to pre-operative chemotherapy: A report of 2 cases.

INTRODUCTION: Majority of Wilms tumour (WT) responds well to pre-operative chemotherapy. In Malaysia, incidence of WT is rare with only two cases reported per one million populations yearly. This case report is to highlight on the awareness of WT in an Asian population and highlight two cases and challenges faced after pre-operative chemotherapy. CASE REPORT: In this case series, we report on two cases of WT which had poor response to pre-operative chemotherapy. Both cases underwent surgery after pre-operative chemotherapy and recovery was uneventful during a two-year follow-up. DISCUSSION: Both patients had chemotherapy prior planned surgery, but had unfortunate poor tumour response. The tumour progressed in size which required a radical nephrectomy. The histology report for the first case had more than 60% blastemal cells remaining despite giving pre-operative chemotherapy with no focal anaplasia. This showed poor response to chemotherapy evidenced by the high number of blastemal cells. The second case was a stromal type WT which is known for poor response and may lead to enhancement of growth and maturation induced by chemotherapy. These were the possible reason of poor response of WT in these two cases.

Positive-Parity Linear-Chain Molecular Band in

An inelastic excitation and cluster-decay experiment ^{2}H(^{16}C,^{4}He+^{12}Be or ^{6}He+^{10}Be)^{2}H was carried out to investigate the linear-chain clustering structure in neutron-rich ^{16}C. For the first time, decay paths from the ^{16}C resonances to various states of the final nuclei were determined, thanks to the well-resolved Q-value spectra obtained from the threefold coincident measurement. The close-threshold resonance at 16.5 MeV is assigned as the J^{π}=0^{+} band head of the predicted positive-parity linear-chain molecular band with (3/2_{π}^{-})^{2}(1/2_{σ}^{-})^{2} configuration, according to the associated angular correlation and decay analysis. Other members of this band were found at 17.3, 19.4, and 21.6 MeV based on their selective decay properties, being consistent with the theoretical predictions. Another intriguing high-lying state was observed at 27.2 MeV which decays almost exclusively to ^{6}He+^{10}Be(∼6 MeV) final channel, corresponding well to another predicted linear-chain structure with the pure σ-bond configuration.

Intrauterine contraceptive device embedded in bladder wall with calculus formation removed successfully with open surgery.

An Intrauterine contraceptive devices (IUCD) is commonly inserted by the primary health care physician. It can migrate into pelvic or abdominal organs. When a pregnancy occurs following an insertion of an IUCD, there should be a high suspicion of uterine perforation or possible migration. A radiograph can be done in the primary health care clinic to search for a missing IUCD. Early referral to the urology service is warranted when a patient presents with recurrent urinary tract infections. Removal of an intravesical IUCD can be managed with cystoscopy, laparoscopy or open surgery. Herein, we report a case of IUCD migration into the bladder. This case will highlight the importance of proper technique, careful insertion and the role of ultrasound.

Caecal Volvulus after a dental procedure - not just constipation!

Caecal volvulus has been reported to be associated with various abdominal and pelvic pathologies. Its signs and symptoms are usually non-specific and maybe overlooked in favour of benign causes, such as constipation. A high degree of suspicion is required for prompt diagnosis. Herein, we report on an unusual case of caecal volvulus after a dental procedure that was managed initially as constipation.

External validation of a modified trauma and injury severity score model in major trauma injury.

BACKGROUND: The establishment of an accurate prognostic model in major trauma patients is important mainly because this group of patients will benefit the most. Clinical prediction models must be validated internally and externally on a regular basis to ensure the prediction is accurate and current. This study aims to externally validate two prediction models, the Trauma and Injury Severity Score model developed using the Major Trauma Outcome Study in North America (MTOS-TRISS model), and the NTrD-TRISS model, which is a refined MTOS-TRISS model with coefficients derived from the Malaysian National Trauma Database (NTrD), by regarding mortality as the outcome measurement. METHOD: This retrospective study included patients with major trauma injuries reported to a trauma centre of Hospital Sultanah Aminah over a 6-year period from 2011 and 2017. Model validation was examined using the measures of discrimination and calibration. Discrimination was assessed using the area under the receiver operating characteristic curve (AUC) and 95% confidence interval (CI). The Hosmer-Lemeshow (H-L) goodness-of-fit test was used to examine calibration capabilities. The predictive validity of both MTOS-TRISS and NTrD-TRISS models were further evaluated by incorporating parameters such as the New Injury Severity Scale and the Injury Severity Score. RESULTS: Total patients of 3788 (3434 blunt and 354 penetrating injuries) with average age of 37 years (standard deviation of 16 years) were included in this study. All MTOS-TRISS and NTrD-TRISS models examined in this study showed adequate discriminative ability with AUCs ranged from 0.86 to 0.89 for patients with blunt trauma mechanism and 0.89 to 0.99 for patients with penetrating trauma mechanism. The H-L goodness-of-fit test indicated the NTrD-TRISS model calibrated as good as the MTOS-TRISS model for patients with blunt trauma mechanism. CONCLUSION: For patients with blunt trauma mechanism, both the MTOS-TRISS and NTrD-TRISS models showed good discrimination and calibration performances. Discrimination performance for the NTrD-TRISS model was revealed to be as good as the MTOS-TRISS model specifically for patients with penetrating trauma mechanism. Overall, this validation study has ascertained the discrimination and calibration performances of the NTrD-TRISS model to be as good as the MTOS-TRISS model particularly for patients with blunt trauma mechanism.

[National experts consensus on tracheotomy and intubation for burn patients (2018 version)].

Airway edema, stenosis, obstruction and even asphyxia are easy to occur in patients with extensive burn, deep burn of head, face, and neck area, inhalation injuries, etc., which threaten life. Timely tracheotomy and intubation is an important treatment measure, but lack of knowledge and improper handling in some hospitals resulted in airway obstruction. The technique of percutaneous tracheotomy and intubation provides convenience for emergency treatment of critical burns and mass burn. The Burn and Trauma Branch of Chinese Geriatrics Society organized some experts in China to discuss the indications, timing, methods, extubation, and precautions of tracheotomy and intubation for burn patients. The national experts consensus on tracheotomy and intubation for burn patients (2018 version) was written to provide a reference standard for clinical treatment.

[National experts consensus on tracheotomy and intubation for burn patients (2018 version)].

Airway edema, stenosis, obstruction and even asphyxia are easy to occur in patients with extensive burn, deep burn of head, face, and neck area, inhalation injuries, etc., which threaten life. Timely tracheotomy and intubation is an important treatment measure, but lack of knowledge and improper handling in some hospitals resulted in airway obstruction. The technique of percutaneous tracheotomy and intubation provides convenience for emergency treatment of critical burns and mass burn. The Chinese Geriatrics Society organized some experts in China to discuss the indications, timing, methods, extubation, and precautions of tracheotomy and intubation for burn patients. The national experts consensus on tracheotomy and intubation for burn patients (2018 version) was written to provide a reference standard for clinical treatment.

Orbital decompression for thyroid eye disease: methods, outcomes, and complications.

PurposeTo determine the safety and effectiveness of orbital decompression for thyroid eye disease (TED) in our unit. To put this in the context of previously published literature.Patients and methodsA retrospective case review of all patients undergoing orbital decompression for TED under the care of one orbital surgeon (SMS) between January 2009 and December 2015. A systematic literature review of orbital decompression for TED.ResultsWithin the reviewed period, 93 orbits of 55 patients underwent decompression surgery for TED. There were 61 lateral (single) wall decompressions, 17 medial one-and-a-half wall, 11 two-and-a-half wall, 2 balanced two wall, and 2 orbital fat only decompressions. For the lateral (single) wall decompressions, mean reduction in exophthalmometry (95% confidence interval (CI) was 4.2 mm (3.7-4.8), for the medial one-and-a-half walls it was 2.9 mm (2.1-3.7), and for the two-and-a-half walls it was 7.6 mm (5.8-9.4). The most common complications were temporary postoperative numbness (29% of lateral decompressions, 17% of other bony decompressions, OR 0.50, 95% CI 0.12-2.11) and new postoperative diplopia (9% of lateral decompressions, 39% of other bony decompressions, OR 6.8, 95% CI 1. 5-30.9). Systematic literature searching showed reduction in exophthalmometry for lateral wall surgery of 3.6-4.8 mm, with new diplopia 0-38% and postoperative numbness 12-50%. For other bony decompressions, reduction in exophthalmometry was 2.5-8.0 mm with new diplopia 0-45% and postoperative numbness up to 52%.ConclusionDiffering approaches to orbital decompression exist. If the correct type of surgery is chosen, then safe, adequate surgical outcomes can be achieved.

Multiple limb salvage attempts for diabetic foot infections: is it worth it?

AIMS: Limb salvage for diabetic foot infections often require multiple procedures. Some patients will eventually end up with below knee amputation (BKA) when all limb salvage attempts fail. We seek to study the patients' ability to return to normal life, functional status, prosthesis usage and perspectives on multiple limb salvage procedures that culminated in BKA to review if they would undertake a similar path if their situation was repeated. PATIENTS AND METHODS: A total of 41 patients who underwent BKA between July 2011 and June 2013 were reviewed. They were divided into primary and creeping (prior multiple salvage procedures) amputations. The Barthel's Index (BI) and the Reintegration to Normal Living Index (RNLI) were used. A questionnaire was used to identify whether the patient would undergo the same multiple attempts at limb salvage again if faced with the same problem. RESULTS: All patients had a good mean BI of 14.2 (3 to 20) and RNLI of 73.2 (31 to 100). There was no difference in prosthesis usage, BI and RNLI between both groups. We found that 16 (94.1%) out of 17 patients with creeping amputation would undergo the same multiple salvage procedures if given a similar option. Conversely, only 15 (62.5%) patients with primary amputation would do the same again while the other nine (37.5%) patients choose to do everything possible to save their leg if faced with a similar situation (p = 0.001). CONCLUSION: Most patients preferred to undergo multiple procedures to salvage the limb from diabetic foot infection even if it ultimately concluded with a BKA. All the patients had a moderately good functional outcome and ability to return to normal living after BKA. Cite this article: Bone Joint J 2017;99-B:1502-7.