COVID-19 vaccination and transmission patterns among pregnant and postnatal women during the fifth wave of COVID-19 in a tertiary hospital in Hong Kong.

INTRODUCTION: Vaccination is a key strategy to control the coronavirus disease 2019 (COVID-19) pandemic. Safety concerns strongly influence vaccine hesitancy. Disease transmission during pregnancy could exacerbate risks of preterm birth and perinatal mortality. This study examined patterns of vaccination and transmission among pregnant and postnatal women during the fifth wave of COVID-19 in Hong Kong. METHODS: The Antenatal Record System and Clinical Management System of the Hospital Authority was used to retrieve information concerning the demographic characteristics, vaccination history, COVID-19 status, and obstetric outcomes of women who were booked for delivery at Queen Mary Hospital in Hong Kong and had attended the booking antenatal visit from 1 July 2021 to 30 June 2022. RESULTS: Among 2396 women in the cohort, 2006 (83.7%), 1843 (76.9%), and 831 (34.7%) had received the first, second, and third doses of COVID-19 vaccine, respectively. Among 1012 women who had received the second dose, 684 (67.6%) women were overdue for their third dose. There were 265 (11.1%) reported COVID-19 cases. Women aged 20 to 29 years had a low vaccination rate but the highest disease rate (19.1%). The disease rate was more than tenfold higher in women who had no (20.3%) or incomplete (18.8%) vaccination, compared with women who had complete vaccination (2.1%; P<0.001). CONCLUSION: Acceptance of COVID-19 vaccination was low in pregnant women. Urgent measures are needed to promote vaccination among pregnant women before the next wave of COVID-19.

Single point mutation on the gene encoding dysbindin results in recognition deficits.

The dystrobrevin-binding protein 1 (DTNBP1) gene is a candidate risk factor for schizophrenia and has been associated with cognitive ability in both patient populations and healthy controls. DTNBP1 encodes dysbindin protein, which is localized to synaptic sites and is reduced in the prefrontal cortex and hippocampus of patients with schizophrenia, indicating a potential role in schizophrenia etiology. Most studies of dysbindin function have focused on the sandy (sdy) mice that lack dysbindin protein and have a wide range of abnormalities. In this study, we examined dysbindin salt and pepper (spp) mice that possess a single point mutation on the Dtnbp1 gene predicted to reduce, but not eliminate, dysbindin expression. By western blot analysis, we found that spp homozygous (spp -/-) mutants had reduced dysbindin and synaptosomal-associated protein 25 (SNAP-25) in the prefrontal cortex, but unaltered levels in hippocampus. Behaviorally, spp mutants performed comparably to controls on a wide range of tasks assessing locomotion, anxiety, spatial recognition and working memory. However, spp -/- mice had selective deficits in tasks measuring novel object recognition and social novelty recognition. Our results indicate that reduced dysbindin and SNAP-25 protein in the prefrontal cortex of spp -/- is associated with selective impairments in recognition processing. These spp mice may prove useful as a novel mouse model to study cognitive deficits linked to dysbindin alterations. Our findings also suggest that aspects of recognition memory may be specifically influenced by DTNBP1 single nucleotide polymorphisms or risk haplotypes in humans and this connection should be further investigated.

Preference of Food Saltiness and Willingness to Consume Low-Sodium Content Food in a Chinese Population.

OBJECTIVE: To compare the preference of food saltiness and the willingness to consume low-sodium food among hypertensive older people, non-hypertensive older people and non-hypertensive young people in a Chinese population. DESIGN: A cross-sectional study based on a quota sample. Three saltiness options (low-sodium, medium-sodium and high-sodium) of soup and bread were offered to each participant who rated the taste of each food on a 5-point Likert scale. Then, the participants rated their willingness to consume the low-sodium content foods on a 5-point Likert scale, given they were informed of the benefit of the low-sodium option. Generalised linear mixed model and multiple linear regression were used to analyse the data. SETTING: Elderly centres and community centres in Hong Kong. PARTICIPANTS: Sixty hypertensive older people, 49 non-hypertensive older people and 60 non-hypertensive young people were recruited from June to August 2014. MEASUREMENTS: The tastiness score and the willingness score were the primary outcome measures. The Chinese Health Literacy Scale for Low Salt Consumption - Hong Kong population (CHLSalt-HK) was also assessed. RESULTS: The tastiness rating of the high-sodium option of soup was significantly lower than the medium-sodium option (p<0.001), but there was no significant difference between the low-sodium and the medium-sodium options (p=0.204). For bread, tastiness rating of the low-sodium option and the high-sodium option were significantly lower than the medium-sodium option (p<0.001 for both options). The tastiness score of soup did not have significant difference across the groups (p=0.181), but that of bread from the hypertensive older adults (p=0.012) and the non-hypertensive older adults (p=0.006) was significantly higher than the non-hypertensive young adults. Higher willingness rating to consume the low-sodium option was significantly (p<0.001) associated with higher tastiness rating of the low-sodium option of soup and bread, and weakly associated with higher health literacy of low salt intake (soup: p=0.041; bread: p=0.024). Hypertensive older adults tended to be more willing to consume the low-sodium option than non-hypertensive older adults for soup (p=0.009), there was insignificant difference between non-hypertensive older adults and non-hypertensive young adults (p=0.156). For bread, there was insignificant difference in willingness rating to consume low-sodium option (p=0.375). CONCLUSION: Older people are at a higher risk of hypertension, reduction of salt intake is important for them to reduce their risk of cardiovascular diseases. There is room for reducing the sodium content of soup, while the sodium in bread should be reduced progressively. Improving the taste of low-sodium food may help to promote reduction in dietary sodium intake.

Strategic evaluation of vaccine candidate antigens for the prevention of Visceral Leishmaniasis.

Infection with Leishmania parasites results in a range of clinical manifestations and outcomes, the most severe of which is visceral leishmaniasis (VL). Vaccination will likely provide the most effective long-term control strategy, as the large number of vectors and potential infectious reservoirs renders sustained interruption of Leishmania parasite transmission extremely difficult. Selection of the best vaccine is complicated because, although several vaccine antigen candidates have been proposed, they have emerged following production in different platforms. To consolidate the information that has been generated into a single vaccine platform, we expressed seven candidates as recombinant proteins in E. coli. After verifying that each recombinant protein could be recognized by VL patients, we evaluated their protective efficacy against experimental L. donovani infection of mice. Administration in formulation with the Th1-potentiating adjuvant GLA-SE indicated that each antigen could elicit antigen-specific Th1 responses that were protective. Considering the ability to reduce parasite burden along with additional factors such as sequence identity across Leishmania species, we then generated a chimeric fusion protein comprising a combination of the 8E, p21 and SMT proteins. This E. coli -expressed fusion protein was also demonstrated to protect against L. donovani infection. These data indicate a novel recombinant vaccine antigen with the potential for use in VL control programs.

Influence of Intermittent Preventive Treatment on Antibodies to VAR2CSA in Pregnant Cameroonian Women.

Intermittent preventive treatment (IPT) and insecticide-treated bed nets are the standard of care for preventing malaria in pregnant women. Since these preventive measures reduce exposure to malaria, their influence on the antibody (Ab) response to the parasite antigen VAR2CSA was evaluated in pregnant Cameroonian women exposed to holoendemic malaria. Ab levels to full-length VAR2CSA (FV2), variants of the six Duffy binding like (DBL) domains, and proportion of high avidity Ab to FV2 were measured longitudinally in 92 women before and 147 women after IPT. As predicted, reduced exposure interfered with acquisition of Ab in primigravidae, with 71% primigravidae being seronegative to FV2 at delivery. Use of IPT for > 13 weeks by multigravidae resulted in 26% of women being seronegative at delivery and a significant reduction in Ab levels to FV2, DBL5, DBL6, proportion of high avidity Ab to FV2, and number of variants recognized. Thus, in women using IPT important immune responses were not acquired by primigravidae and reduced in a portion of multigravidae, especially women with one to two previous pregnancies. Longitudinal data from individual multigravidae on IPT suggest that lower Ab levels most likely resulted from lack of boosting of the VAR2CSA response and not from a short-lived Ab response.

Predictors of Chest Wall Toxicity after Lung Stereotactic Ablative Radiotherapy.

AIMS: To determine the incidence and predictive factors of rib fracture and chest wall pain after lung stereotactic ablative radiotherapy (SABR). MATERIALS AND METHODS: Patients were treated with lung SABR of 48-60 Gy in four to five fractions. The treatment plan and follow-up computed tomography scans of 289 tumours in 239 patients were reviewed. Dose-volume histogram (DVH) metrics and clinical factors were evaluated as potential predictors of chest wall toxicity. RESULTS: The median follow-up was 21.0 months (range 6.2-52.1). Seventeen per cent (50/289) developed a rib fracture, 44% (22/50) were symptomatic; the median time to fracture was 16.4 months. On univariate analysis, female gender, osteoporosis, tumours adjacent (within 5 mm) to the chest wall and all of the chest wall DVH metrics predicted for rib fracture, but only tumour location adjacent to the chest wall remained significant on the multivariate model (P < 0.01). The 2 year fracture-free probability for those adjacent to the chest wall was 65.6%. Among those tumours adjacent to the chest wall, only osteoporosis (P = 0.02) predicted for fracture, whereas none of the chest wall DVH metrics were predictive. Eight per cent (24/289) experienced chest wall pain without fracture. CONCLUSIONS: None of the chest wall DVH metrics independently predicted for SABR-induced rib fracture when tumour location is taken into account. Patients with tumours adjacent (within 5 mm) to the chest wall are at greater risk of rib fracture after lung SABR, and among these, an additional risk was observed in osteoporotic patients.

Development and comparative evaluation of two antigen detection tests for Visceral Leishmaniasis.

BACKGROUND: Visceral leishmaniasis (VL) can be fatal without timely diagnosis and treatment. Treatment efficacies vary due to drug resistance, drug toxicity and co-morbidities. It is important to monitor treatment responsiveness to confirm cure and curtail relapse. Currently, microscopy of spleen, bone marrow or lymph node biopsies is the only definitive method to evaluate cure. A less invasive test for treatment success is a high priority for VL management. METHODS: In this study, we describe the development of a capture ELISA based on detecting Leishmania donovani antigens in urine samples and comparison with the Leishmania Antigen ELISA, also developed for the same purpose. Both were developed as prototype kits and tested on patient urine samples from Sudan, Ethiopia, Bangladesh and Brazil, along with appropriate control samples from endemic and non-endemic regions. Sensitivity and specificity were assessed based on accurate detection of patients compared to control samples. One-Way ANOVA was used to assess the discrimination capacity of the tests and Cohen's kappa was used to assess their correlation. RESULTS: The Leishmania Antigen Detect ELISA demonstrated >90% sensitivity on VL patient samples from Sudan, Bangladesh and Ethiopia and 88% on samples from Brazil. The Leishmania Antigen ELISA was comparable in performance except for lower sensitivity on Sudanese samples. Both were highly specific. To confirm utility in monitoring treatment, urine samples were collected from VL patients at days 0, 30 and 180 post-treatment. For the Leishmania Antigen Detect ELISA, positivity was high at day 0 at 95%, falling to 21% at day 30. At day 180, all samples were negative, corresponding well with clinical cure. A similar trend was also seen for the Leishmania Antigen ELISA albeit; with lower positivity of 91% at Day 0 and more patients, remaining positive at Days 30 and 180. DISCUSSION: The Leishmania Antigen Detect and the Leishmania Antigen ELISAs are standardized, user- friendly, quantitative and direct tests to detect Leishmania during acute VL as well as to monitor parasite clearance during treatment. They are a clear improvement over existing options. CONCLUSION: The ELISAs provide a non-invasive method to detect parasite antigens during acute infection and monitor its clearance upon cure, filling an unmet need in VL management. Further refinement of the tests with more samples from endemic regions will define their utility in monitoring treatment.

Does long-distance walking improve or deteriorate walking stability of transtibial amputees?

BACKGROUND: Falls are common in transtibial amputees which are linked to their poor stability. While amputees are encouraged to walk more, they are more vulnerable to fatigue which leads to even poorer walking stability. The objective of this study was to evaluate the dynamic stability of amputees after long-distance walking. METHODS: Six male unilateral transtibial amputees (age: 53 (SD: 8.8); height: 170cm (SD: 3.4); weight: 75kg (SD: 4.7)) performed two sessions (30minutes each) of treadmill walking, separated by a short period of gait tests. Gait tests were performed before the walking (baseline) and after each session of treadmill walking. Gait parameters and their variability across repeated steps at each of the three conditions were computed. FINDINGS: There were no significant differences in walking speed, step length, stance time, time of occurrence, and magnitude of peak angular velocities of the knee and hip joint (P>0.05). However, variability of knee and hip angular velocity after 30-minute walking was significantly higher than the baseline (P<0.05) and after a total of 60-minute walking (P<0.05). The variability of lateral sway velocity after 30-minute walking was significantly higher than the baseline (P<0.05). INTERPRETATION: The significant increase in variability after 30-minute walking could indicate poorer walking stability when fatigue was developed, while the significant reduction after 60-minute walking might indicate the ability of amputees to restore their walking stability after further continuous walking.

Predictive factors for local control in primary and metastatic lung tumours after four to five fraction stereotactic ablative body radiotherapy: a single institution's comprehensive experience.

AIMS: We report the outcomes of a large lung stereotactic ablative body radiotherapy (SABR) programme for primary non-small cell lung cancer (NSCLC) and pulmonary metastases. The primary study aim was to identify factors predictive for local control. MATERIALS AND METHODS: In total, 311 pulmonary tumours in 254 patients were treated between 2008 and 2011 with SABR using 48-60 Gy in four to five fractions. Local, regional and distant failure data were collected prospectively, whereas other end points were collected retrospectively. Potential clinical and dosimetric predictors of local control were evaluated using univariate and multivariate analyses. RESULTS: Of the 311 tumours, 240 were NSCLC and 71 were other histologies. The 2 year local control rate was 96% in stage I NSCLC, 76% in colorectal cancer (CRC) metastases and 91% in non-lung/non-CRC metastases. Predictors of better local control on multivariate analysis were non-CRC tumours and a larger proportion of the planning target volume (PTV) receiving ≥100% of the prescribed dose (higher PTV V100). Among the 45 CRC metastases, a higher PTV V100 and previous chemotherapy predicted for better local control. CONCLUSIONS: Lung SABR of 48-60 Gy/four to five fractions resulted in high local control rates for all tumours except CRC metastases. Covering more of the PTV with the prescription dose (a higher PTV V100) also resulted in superior local control.

Evaluation of the Microsoft Kinect as a clinical assessment tool of body sway.

Total body center of mass (TBCM) is a useful kinematic measurement of body sway. However, expensive equipment and high technical requirement limit the use of motion capture systems in large-scale clinical settings. Center of pressure (CP) measurement obtained from force plates cannot accurately represent TBCM during large body sway movement. Microsoft Kinect is a rapidly developing, inexpensive, and portable posturographic device, which provides objective and quantitative measurement of TBCM sway. The purpose of this study was to evaluate Kinect as a clinical assessment tool for TBCM sway measurement. The performance of the Kinect system was compared with a Vicon motion capture system and a force plate. Ten healthy male subjects performed four upright quiet standing tasks: (1) eyes open (EOn), (2) eyes closed (ECn), (3) eyes open standing on foam (EOf), and (4) eyes closed standing on foam (ECf). Our results revealed that the Kinect system produced highly correlated measurement of TBCM sway (mean RMSE=4.38 mm; mean CORR=0.94 in Kinect-Vicon comparison), as well as comparable intra-session reliability to Vicon. However, the Kinect device consistently overestimated the 95% CL of sway by about 3mm. This offset could be due to the limited accuracy, resolution, and sensitivity of the Kinect sensors. The Kinect device was more accurate in the medial-lateral than in the anterior-posterior direction, and performed better than the force plate in more challenging balance tasks, such as (ECf) with larger TBCM sway. Overall, Kinect is a cost-effective alternative to a motion capture and force plate system for clinical assessment of TBCM sway.

Patterns of cortical activation following motor tasks and psychological-inducing movie cues in heroin users: an fMRI study.

OBJECTIVE: Drug abuse and addiction are worldwide health problems. However, few studies have used fMRI to investigate the effect of chronic heroin use on brain activation. This is a study along this line. METHOD: fMRI positive sites in the brain were recorded during different motor and sensory activities. RESULTS: Following motor activities, heroin users had more sites globally activated in the brain than in normal volunteers, with ex-heroin users being least reactive. Conversely, a "heroin puffing" movie produced more activation in ongoing-heroin and ex-heroin users than in the normal individuals, whereas a movie with explicit sexual content was less stimulatory in both groups of heroin users compared to normal individuals. CONCLUSIONS: These significant findings relative to the function of specific brain nuclei are discussed.

A rapid ELISA for the diagnosis of MB leprosy based on complementary detection of antibodies against a novel protein-glycolipid conjugate.

Despite the widespread use of multidrug therapy for treatment, delays in clinical recognition and under-reporting of leprosy indicate that Mycobacterium leprae transmission is continuing. Thus, leprosy is likely to persist as a significant burden on health systems in many regions. In this study, we combined 2 previously characterized leprosy antigens, leprosy IDRI diagnostic-1 (LID-1) and ND-O, into the single fusion complex (ND-O-LID) and determined the serum antibody responses of leprosy patients from Colombia and the Philippines. Following confirmation that antibodies recognized each component within the conjugate, we assessed the performance of a rapid enzyme-linked immunosorbent assay (ELISA) system (Leprosy Detect(TM) fast ELISA; InBios International, Inc., Seattle, WA, USA) based on ND-O-LID capable of generating results within 1.5hours of sample addition. We found ELISA results correlated with the bacteriological index and Ridley-Jopling categorization, with lepromatous leprosy patients having the highest responses, while those of borderline tuberculoid patients were lower. Multibacillary (MB) leprosy patients were distinguished with a high degree of sensitivity (95.7%) and specificity (93.2%), suggesting that this ELISA could potentially replace invasive and insensitive skin slit smear procedures that require expert microscopic examinations. Due to the speed and robustness of this assay, we believe this is an excellent tool for detecting MB leprosy patients in a simple and highly-quantitative manner.

Chronic hepatitis B virus (HBV) infection in children: 25 years' experience.

Whereas e-seroconversion represents the loss of hepatitis B e-antigen (HBeAg) followed by gain of antibody to HBeAg (anti-HBe), 'inactive chronic infection' extends this concept to include e-seroconversion with decreased serum viral load and biochemical remission. These events must be well-characterized before treatment outcomes can be evaluated. We examined the rates of e-seroconversion and achievement of inactive chronic infection among children with chronic HBV infection. Children who were HBsAg positive >6 months were identified retrospectively between 1983 and 2008 from the Hospital for Sick Children Liver Clinic. Inactive chronic infection was defined as loss of HBeAg, serum ALT ≤40 IU/mL, and HBV DNA <10(6 ) IU/mL. Both e-seroconversion and achievement of inactive chronic infection were characterized using survival analysis. The effect of transmission route, treatment, age at diagnosis, ethnicity, gender and baseline ALT on these rates was evaluated with univariate and multiple regression. Of 252 HBeAg-positive cases, 59.9% had HBV-infected mothers, 77% were Asian, and 33 received interferon-α. Untreated children were younger at last follow-up (mean 14.5 vs 17.6 years), had lower ALT (median 60 vs 116 IU/mL) and had shorter follow-up (6.6 vs 9.1 years, all P < 0.002) compared to treated children. Crude e-seroconversion rate was 41.7% over 0.5-19.1 years of follow-up, and this was not affected by transmission route (P = 0.93), gender (P = 0.62) nor treatment (P = 0.08). 49% achieved inactive chronic infection by age 19 years. Being non-Asian, age at diagnosis<3 years, and ALT ≥40 IU/mL were associated with a higher rate of e-seroconversion and achieving inactive chronic infection (P < 0.0001). Almost 50% of children achieved inactive chronic infection by early adulthood.

Effects of heel lifting on transtibial amputee gait before and after treadmill walking: a case study.

BACKGROUND: Prosthetic alignment is usually unchanged once optimized. However, a previous study indicated that long-distance walking significantly altered gait patterns, suggesting some alignment adjustments after walking are required. This study investigated the effects of alignment changes (by inserting a heel lift) on gait of a transtibial amputee before and after treadmill walking. CASE DESCRIPTION AND METHODS: The subject walked, without heel lifts, on a treadmill until perception of fatigue. Gait changes upon heel lifting at the prosthetic side were studied before and after the treadmill walking FINDINGS AND OUTCOMES: For this subject before the treadmill walking, heel lifting induced drop-off with increased prosthetic-side knee flexion at mid-stance and pre-swing. The sound limb outreached to stabilize the gait. After the treadmill walking, the same heel lift did not induce drop-off. It reduced the plantar flexor power generation, potentially delaying its fatigue. CONCLUSION: After walking prosthetic-side heel lifting could be beneficial. CLINICAL RELEVANCE: Many lower-limb amputees have difficulties in long-distance walking due to muscle fatigue. This case study proposes that appropriate alignment changes after some walking potentially relieve fatigue and encourage them to walk longer distances.

Effects of long-distance walking on socket-limb interface pressure, tactile sensitivity and subjective perceptions of trans-tibial amputees.

PURPOSE: Many trans-tibial amputees could not tolerate long-distance walking. Lack of walking could explain for the increased cardiovascular diseases mortality rate. This study investigated the effects of long-distance walking (LDW) on socket-limb interface pressure, tactile sensitivity of the residual limb, and subjective feedbacks, which potentially identified the difficulties in LDW. METHOD: Five male unilateral trans-tibial amputees walked on a level treadmill for a total of one hour at comfortable speed. Tactile sensitivity of the residual limb and socket-limb interface pressure during over-ground walking were measured before and after the treadmill walking. Modified Prosthesis Evaluation Questionnaires were also administered. RESULTS: After the treadmill walking, the socket-limb interface pressure and the tactile sensitivity at the popliteal depression area were significantly reduced. This corresponds well with the questionnaire results showing that the level of discomfort and pain of the residual limb did not increase. The questionnaire revealed that there were significant increases in fatigue level at the sound-side plantar flexors, which could lead to impaired dynamic stability. CONCLUSIONS: Fatigue of sound-side plantar-flexor was the main difficulty faced by the five subjects when walking long-distances. This finding might imply the importance of refining prosthetic components and rehabilitation protocols in reducing the muscle fatigue. IMPLICATIONS FOR REHABILITATION: • After long-distance walking (LDW) of the trans-tibal amputee subjects, there were significant increases in fatigue level at the plantar flexors. These might explain the reduced walking stability as perceived by the subjects. • LDW did not produce any problems in residual-limb comfort and pain feeling. These were in line with the significant reductions of socket-limb interface pressure and the tactile sensitivity at the popliteal depression after LDW. • Refinements of prosthetic components and rehabilitation protocols should be attempted to reduce the fatigue of the plantar flexors and facilitate LDW.

International variability in the reimbursement of cancer drugs by publically funded drug programs.

PURPOSE: Evaluate inter-country variability in the reimbursement of publically funded cancer drugs, and identify factors such as cost containment measures that may contribute to variability. METHODS: As of February 28, 2010, licensed indications for 10 cancer drugs (bevacizumab, bortezomib, cetuximab, erlotinib, imatinib, pemetrexed, rituximab, sorafenib, sunitinib, and trastuzumab) were obtained from the drug registries of 6 licensing authorities corresponding to 13 countries or regions: Australia, Canada (Ontario), England, Finland, France, Italy, Germany, Japan, New Zealand, the Netherlands, Scotland, Sweden, and the United States (Medicare Parts B and D). Number of licensed indications reimbursed by public payers and the use of cost containment measures were obtained by survey of health authorities involved in reimbursement and through public documents. RESULTS: The 48 identified licensed indications varied between agencies (range: 36-44 indications). Finland, France, Germany, Sweden, and the United States reimbursed the highest percentage of indications (range: 90%-100%). Canada (54%), Australia (46%), Scotland (40%), England (38%), and New Zealand (25%) reimbursed the least. All 5 countries with the lowest rate of reimbursement incorporated a cost-effectiveness analysis into reimbursement decisions and rejected submissions for reimbursement mainly because of lack of cost effectiveness; in New Zealand, lack of cost effectiveness was the second leading cause of rejection after excessive cost. In 9 countries, risk-sharing agreements were used to contain costs. Indications initially not recommended for reimbursement (9 in Australia, 5 in Canada, and 3 in England, New Zealand, and Scotland) were subsequently approved with risk-sharing agreements or special pricing arrangements. CONCLUSIONS: Reimbursement of publically funded cancer drugs varies globally. The cause is multifactorial.

High levels of antibodies to multiple domains and strains of VAR2CSA correlate with the absence of placental malaria in Cameroonian women living in an area of high Plasmodium falciparum transmission.

Placental malaria, caused by sequestration of Plasmodium falciparum-infected erythrocytes in the placenta, is associated with increased risk of maternal morbidity and poor birth outcomes. The parasite antigen VAR2CSA (variant surface antigen 2-chondroitin sulfate A) is expressed on infected erythrocytes and mediates binding to chondroitin sulfate A, initiating inflammation and disrupting homeostasis at the maternal-fetal interface. Although antibodies can prevent sequestration, it is unclear whether parasite clearance is due to antibodies to a single Duffy binding-like (DBL) domain or to an extensive repertoire of antibodies to multiple DBL domains and allelic variants. Accordingly, plasma samples collected longitudinally from pregnant women were screened for naturally acquired antibodies against an extensive panel of VAR2CSA proteins, including 2 to 3 allelic variants for each of 5 different DBL domains. Analyses were performed on plasma samples collected from 3 to 9 months of pregnancy from women living in areas in Cameroon with high and low malaria transmission. The results demonstrate that high antibody levels to multiple VAR2CSA domains, rather than a single domain, were associated with the absence of placental malaria when antibodies were present from early in the second trimester until term. Absence of placental malaria was associated with increasing antibody breadth to different DBL domains and allelic variants in multigravid women. Furthermore, the antibody responses of women in the lower-transmission site had both lower magnitude and lesser breadth than those in the high-transmission site. These data suggest that immunity to placental malaria results from high antibody levels to multiple VAR2CSA domains and allelic variants and that antibody breadth is influenced by malaria transmission intensity.

Long-distance walking effects on trans-tibial amputees compensatory gait patterns and implications on prosthetic designs and training.

Trans-tibial amputees are advised to walk as much as able people to achieve healthy and independent life. However, they usually have difficulties in doing so. Previous researches only included data from a few steps when studying the gait of amputees. Walking over a long distance was rarely examined. The objective of this study was to investigate the changes in spatial-temporal, kinetic and kinematic gait parameters of trans-tibial amputees after long-distance walking. Six male unilateral trans-tibial amputees performed two sessions of 30-min walking on a level treadmill at their self-selected comfortable speed. Gait analysis was undertaken over-ground: (1) before walking, (2) after the 1st walking session and (3) after the 2nd walking session. After the long-distance walking, changes in spatial-temporal gait parameters were small and insignificant. However, the sound side ankle rocker progression and push-off were significantly reduced. This was due to the fatigue of the sound side plantar flexors and was compensated by the greater effort in the prosthetic side. The prosthetic side knee joint showed significantly increased flexion and moment during loading response to facilitate the anterior rotation of the prosthetic shank. The prosthetic side hip extensors also provided more power at terminal stance to facilitate propulsion. Endurance training of the sound side plantar flexors, and improvements in the prosthetic design to assist anterior rotation of the prosthetic shank should improve long-distance walking in trans-tibial amputees.

Ketamine effects on the urogenital system--changes in the urinary bladder and sperm motility.

Different doses of ketamine (10 mg/kg, 20 mg/kg, 30 mg/kg, 40 mg/kg, 50 mg/kg, and 60 mg/kg) were injected i.p. (I.P.), respectively, to male ICR mice to determine the optimal dosage for chronic administration. At and above 40 mg/kg I.P. injection, mice had almost no hindlimb movement during swimming test. Subsequently, 30 mg/kg was used as the dose for the study in the toxicity of long-term ketamine administration on urinary bladder and sperm motility. The treatment group were subdivided into two (n = 10 each group); one received daily ketamine treatment i.p. for 3 months and another group for 6 months. Corresponding number of mice in control groups (n = 5 each group) received saline injection instead of ketamine. Terminal dUTP nick and labeling (TUNEL) study and Sirius red staining were carried out on the sectioned slides of the urinary bladders to study the degree of apoptosis in both epithelium and muscular layers of the urinary bladder and the relative thickness of the muscular layers in this organ was also computed. Apoptosis in the bladder epithelium was observed initially in the 3-month ketamine treated mice and the number of apoptotic cells was significantly different (P < 0.05) between the 3-month and 6-month ketamine treated mice and the control. The relative thickness of muscular layers in the bladder wall also decreased significantly (P < 0.05) when the 6-month treated mice and the control were compared. Sirius red staining revealed increase of collagen in the urinary bladder of the treated mice, most evidently 6 months after ketamine treatment. In addition, the sperm motility was studied and there was a statistically significant difference between the control and ketamine treated groups in the percentages of sperms which were motile (P < 0.05). This suggested that the chronic administration of ketamine affected the genital system as well.

Localization of 5-HT1A and 5-HT2A positive cells in the brainstems of control age-matched and Alzheimer individuals.

Serotonin receptor 1A and 2A positive cells in postmortem brainstems were demonstrated via immunohistochemistry in eight control age-matched elderly individuals and eight Alzheimer patients. The 5-HT1A positive cells were found in substantia nigra, pontile nucleus, and vagal as well as dorsal raphe nucleus, while 5-HT2A receptor positive cells were found in motor, sensory and spinal trigeminal nuclei, pontile nucleus, substantia nigra, and nucleus solitarius. A comparison in density of positive cells per unit area was made between control age-matched and Alzheimer individuals. Statistically significant differences (p ≤ 0.01) in density were observed in 5-HT1A cells in pontile, dorsal raphe, and vagal nuclei between control age-matched and Alzheimer, and in 5-HT2A positive cells in the sensory trigeminal nucleus, between control and Alzheimer. This de novo study indicated the presence of 5-HT1A and 5-HT2A receptor positive cells in the above nuclei of human brainstem and revealed differences in density between control age-matched and Alzheimer, indicating possible functional derangements in Alzheimer patients in these areas. In addition, colocalization studies indicated that 5-HT1A receptors were in cholinergic cells and gamma-aminobutyric acid positive fibers were linked to 5-HT2A receptor positive cells. It is hoped that understanding these two important 5-HT receptors and their localization might lead to advances in future therapeutic development.