Scaphoid, lunate and capitate kinematics in the normal and ligament deficient wrist: A bi-plane X-ray fluoroscopy study.

The ligamentous structures of the wrist stabilise and constrain the interactions of the carpal bones during active wrist motion; however, the three-dimensional translations and rotations of the scaphoid, lunate and capitate in the normal and ligament deficient wrist during planar and oblique wrist motions remain poorly understood. This study employed a computer-controlled simulator to replicate physiological wrist motion by dynamic muscle force application, while carpal kinematics were simultaneously measured using bi-plane x-ray fluoroscopy. The aim was to quantify carpal kinematics in the native wrist and after sequential sectioning of the scapholunate interosseous ligament (SLIL) and secondary scapholunate ligament structures. Seven fresh-frozen cadaveric wrist specimens were harvested, and cycles of flexion-extension, radial-ulnar deviation and dart-thrower's motion were simulated. The results showed significant rotational and translational changes to these carpal bones in all stages of disruptions to the supporting ligaments (p < 0.05). Specifically, following the disruption of the dorsal SLIL (Stage II), the scaphoid became significantly more flexed, ulnarly deviated, and pronated relative to the radius, whereas the lunate became more extended, supinated and volarly translated (p < 0.05). Sectioning of the dorsal intercarpal (DIC), dorsal radiocarpal (DRC), and scaphotrapeziotrapezoid (STT) ligaments (Stage IV) caused the scaphoid to collapse further into flexion, ulnar deviation, and pronation. These findings highlight the importance of all the ligamentous attachments that relate to the stability of the scapholunate joint, but more importantly, the dorsal SLIL in maintaining scapholunate stability, and the preservation of the attachments of the DIC and DRC ligaments during dorsal surgical approaches. The findings will be useful in diagnosing wrist pathology and in surgical planning.

Online harms? Suicide-related online experience: a UK-wide case series study of young people who die by suicide.

BACKGROUND: Few studies have examined online experience by young people who die by suicide. METHODS: A 3-year UK-wide consecutive case series of all young people aged 10-19 who died by suicide, based on national mortality data. We extracted information on the antecedents of suicide of 544 of these 595 deaths (91%) from official investigations, mainly inquests. RESULTS: Suicide-related online experience was reported in 24% (n = 128/544) of suicide deaths in young people between 2014 and 2016, equivalent to 43 deaths per year, and was more common in girls than boys (OR 1.87, 95% CI 1.23-2.85, p = 0.003) and those identifying as LGBT (OR 2.35, 95% CI 1.10-5.05, p = 0.028). Searching for information about method was most common (n = 68, 13%), followed by posting suicidal ideas online (n = 57, 10%). Self-harm, bereavement (especially by suicide), social isolation, and mental and physical ill-health were more likely in those known to have suicide-related online experience compared to those who did not. 29 (5%) were bullied online, more often girls (OR 2.84, 1.34-6.04, p = 0.007). Online bullying often accompanied face-to-face bullying (n = 16/29, 67%). CONCLUSIONS: Suicide-related online experience is a common, but likely underestimated, antecedent to suicide in young people. Although its causal role is unclear, it may influence suicidality in this population. Mental health professionals should be aware that suicide-related online experience - not limited to social media - is a potential risk for young patients, and may be linked to experiences offline. For public health, wider action is required on internet regulation and support for children and their families.

Fever as a predictor of adverse outcomes in COVID-19.

BACKGROUND/INTRODUCTION: There are little data on outcomes of COVID-19 patients with the presence of fever compared to the presence of symptoms. AIM: We examined the associations between symptomology, presence of fever and outcomes of a COVID-19 cohort. DESIGN AND METHODS: Between 23 January and 30 April 2020, 554 COVID-19 patients were admitted to a tertiary hospital in Singapore. They were allocated into four groups based on symptomology and fever-Group 1: asymptomatic and afebrile, Group 2: symptomatic but afebrile, Group 3: febrile but asymptomatic and Group 4: symptomatic and febrile. The primary outcomes were intensive care unit (ICU) admissions and mortality. The composite end-point included ICU admissions, mortality or any COVID-19 related end-organ involvement. RESULTS: There were differences in ferritin (P=0.003), C-reactive protein (CRP) levels (P<0.001) and lymphopenia (P=0.033) across all groups, with the most favourable biochemical profile in Group 1, and the least in Group 4. Symptomatic groups (Groups 2 and 4) had higher ICU admissions (1.9% and 6.0%, respectively, P=0.003) than asymptomatic groups (Groups 1 and 3). Composite end-point was highest in Group 4 (24.0%), followed by Group 3 (8.6%), Group 2 (4.8%) and Group 1 (2.4%) (P<0.001). The presence of fever (OR 4.096, 95% CI 1.737-9.656, P=0.001) was associated with the composite end-point after adjusting for age, pulse rate, comorbidities, lymphocyte, ferritin and CRP. Presence of symptoms was not associated with the composite end-point. DISCUSSION/CONCLUSION: In this COVID-19 cohort, presence of fever was a predictor of adverse outcomes. This has implications on the management of febrile but asymptomatic COVID-19 patients.

Scaphocapitate fusion for the treatment of Lichtman stage III Kienböck's disease. Results of a single center study with literature review.

The purpose of this study was to report the outcomes of scaphocapitate fusion without lunate excision for the treatment of stage III Kienböck's disease and to compare these results with historical results of limited wrist arthrodesis and proximal row carpectomy. Clinical and radiographic evaluations were performed preoperatively and at a mean of 5.8-years' follow-up (range 1.5 to 10.5years) on 17 patients with advanced Kienböck's disease (Lichtman stages: IIIA n=4 and IIIB n=13) treated by scaphocapitate fusion without lunate excision between January 2000 and July 2015. The average DASH score was 19 points (range 2 to 61) and the PRWE score was 23 points (range 0 to 77). The average preoperative VAS for pain of 8 was significantly reduced to an average of 4 with activity (P=0.002) and 1 at rest (P=0.001). The flexion/extension arc was 91° and grip strength was 76% of the contralateral side. The preoperative mean modified carpal height ratio decreased significantly to an average of 1.14 at the latest follow-up (P=0.02). The average carpal-ulnar distance ratio was not altered (P=0.89). The radioscaphoid and scapholunate angles were restored to their normal range. Four scaphocapitate joints failed to fuse. No re-operations were performed. Scaphocapitate fusion for advanced Kienböck's disease maintains wrist motion and significantly relieves pain. Lunate excision is not necessary. Based on a literature review, our results were comparable to those of scaphotrapeziotrapezoid fusion. Proximal row carpectomy is still an option when the radius and capitate articular surfaces are free of significant chondral lesions.

Indoor temperature and health: a global systematic review.

OBJECTIVES: The objective of this study was to identify and appraise evidence on the direct and indirect impacts of high indoor temperatures on health; the indoor temperature threshold at which the identified health impacts are observed; and to summarise the evidence for establishing a maximum indoor temperature threshold for health. STUDY DESIGN: This is a systematic literature review and narrative synthesis. METHODS: A review of the published literature using MEDLINE, EMBASE, Global Health, PsycINFO, Maternity and Infant Care, Cochrane Library, CINAHL and GreenFILE databases was conducted. The search criteria were kept broad to capture evidence from all countries and contexts; no date or study design limits were applied, except English language limits. We included studies that specifically measured indoor temperature and examined its effect on physical or mental health outcomes. Evidence was graded using the National Institutes of Health framework. RESULTS: Twenty-two articles were included in the review, including 11 observational, seven cross-sectional and three longitudinal cohort studies and one prospective case-control study. Eight main health effects were described: respiratory, blood pressure, core temperature, blood glucose, mental health and cognition, heat-health symptoms, physical functioning and influenza transmission. Five studies found respiratory symptoms worsened in warm indoor environments, with one reporting indoor temperatures higher than 26 °C, which was associated with increased respiratory distress calls being made to paramedics (odds ratio = 1.63, P = 0.056). Core symptoms of schizophrenia and dementia were found to be significantly exacerbated by indoor heat (the latter above a 26 °C cumulative exposure threshold). The absorption of insulin doses in people with type one diabetes was also significantly accelerated in hot indoor environments. Only five studies reported the temperatures at which health outcomes worsened, with thresholds ranging between 26 °C and 32 °C. However, owing to insufficient data and the heterogeneity of the included studies (design, population, setting, exposure measures, outcomes and location), meta-analysis and an upper threshold determination was not feasible. CONCLUSIONS: High indoor temperatures affect aspects of human health, with the strongest evidence for respiratory health, diabetes management and core schizophrenia and dementia symptoms. Exacerbation of symptoms in warm indoor environments has clinical relevance to at-risk groups and those caring for them. Care staff and facility managers need to be vigilant of high temperatures in care environments and should incorporate indoor overheating into their risk management and sustainability and/or climate change adaptation plans. The indoor temperature threshold at which adverse effects begin to occur remains unclear as studies seldom report the exposure-response relationship over a temperature continuum. Until there is extensive scientific data to support a maximum indoor temperature threshold, 26 °C may be the most suitable indoor temperature for at-risk groups in keeping with the existing guidance documents.

Suicide by mental health in-patients under observation.

BACKGROUND: Observations in psychiatric in-patient settings are used to reduce suicide, self-harm, violence and absconding risk. The study aims were to describe the characteristics of in-patients who died by suicide under observation and examine their service-related antecedents. METHOD: A national consecutive case series in England and Wales (2006-2012) was examined. RESULTS: There were 113 suicides by in-patients under observation, an average of 16 per year. Most were under intermittent observation. Five deaths occurred while patients were under constant observation. Patient deaths were linked with the use of less experienced staff or staff unfamiliar with the patient, deviation from procedures and absconding. CONCLUSIONS: We identified key elements of observation that could improve safety, including only using experienced and skilled staff for the intervention and using observation levels determined by clinical need not resources.

Assessment of normal trapeziometacarpal joint alignment.

The purpose of this study was to determine the alignment of the normal trapeziometacarpal joint and any changes in its alignment with age. Radial, dorsal and dorsoradial subluxation were measured on computerized tomographic scans in 50 joints of 50 adults aged 18 to 62. There were statistically significant correlations between increasing age and dorsoradial subluxation but no significant correlation with dorsal and radial subluxation. Significant dorsoradial subluxation occurs after 46 years of age in the normal trapeziometacarpal joint. A mean dorsoradial subluxation of 21% (range 14%-30%) can be considered normal in this age group.

Lateral thyroid cartilage thyrotomy approach to an embedded paraglottic fishbone.

Fishbones are of particular interest to otolaryngologists. Most fishbones can be removed transorally or via endoscopic guidance. Transcervical neck exploration is occasionally necessary, especially in cases of an embedded foreign body. Computed tomography is the most sensitive and specific imaging modality for identifying embedded fishbones. To our knowledge, this is the first reported case of a laryngeal foreign body embedded in the paraglottic space that was removed using an open approach via a lateral thyroid cartilage window.

Prevalence of overactive bladder syndrome (OABS) among women with gynaecological problems and its risk factors in a tertiary hospital, Negeri Sembilan, Malaysia: Implication for primary healthcare providers.

OBJECTIVE: The objective of this paper was to determine the prevalence of overactive bladder syndrome (OABS) and its risk factors among patients with other gynaecological problems. METHODS: This study was conducted on women aged more than 18 years who attended the gynaecology clinic for various diagnoses other than urinary problems at a tertiary hospital in Negeri Sembilan, Malaysia, for a period of 6 months. Data on patient's profile, symptoms and risk factors for overactive bladder (OAB) were prospectively collected using a structured questionnaire adapted from ICIQ (international consultation on incontinence questionnaire). Exclusion criteria included patients with confirmed diagnosis of stress incontinence or OAB, neurological impairment, gynaecological malignancy and those with a previous history of pelvic radiation. Chi-square test and logistic regression test were used in the statistical analysis. We presented the odds ratio (OR) and 95% confidence interval for each of the OAB symptoms with p-value of 0.05. RESULTS: The prevalence of OAB among the patients (n = 573) in this study was 19.1%. History of giving births to macrosomic babies and presence of utero-vaginal prolapse (UVP) were shown to be significantly associated with OAB in the multivariate analysis. Other factors were advanced age, high parity and menopausal for more than 5 years. More than half of the patients with the symptoms of OAB did not seek treatment, as they did not think it is necessary. CONCLUSION: It is found that the prevalence of OAB is similar with many other studies conducted elsewhere. It was found to be multifactorial, but was highly significantly related with the presence of UVP, especially cystocoele and history of giving births to macrosomic babies.

Health care decision making: cross-cultural analysis of the shift from the autonomous to the relational staff.

This paper addresses three factors that have contributed to shifts in decision making in health care. First, the notion of patient autonomy, which has changed due to the rise of patient-centred approaches in contemporary health care and the re-conceptualization of the physician-patient relationship. Second, the understanding of patient autonomy has broadened to better engage patient participation. Third, the need to develop cross-cultural health care ethics. Our paper shows that the shift in the West from the individual to the relational self indicates an important change in the understanding of autonomy through the lens of culture. Practices that recognize the notion of the relational self allow for a more balanced view of autonomy and a richer conception of moral agency.

Imaging in index finger radial collateral ligament injury: attention to detail really pays....

Radial collateral ligament of the index finger is a rare ligament to rupture. X-ray is generally normal, except for subtle findings of soft tissue swelling and occasionally a small fracture. With continuous advances in imaging, ultrasound and high quality MRI allow clear depiction of small structures including joint capsule and collateral ligaments of even the small joints. This helps in definitive diagnosis and determines the extent of injury, which may affect the treatment options and final outcome. We report a rare case of index finger metacarpo-phalangeal joint radial collateral ligament tear. The subtle X-ray abnormality was chased on ultrasound and the diagnosis was proposed on ultrasound and later confirmed on MRI. We also discuss the imaging findings of this rare entity.

Studies on diuretic and hypouricemic effects of Orthosiphon stamineus methanol extracts in rats.

AIM OF THE STUDY: Orthosiphon stamineus (Labiatae) is a traditional folk medicine widely used in Southeast Asia for the treatment of several kidney disorders, gout and as a diuretic. This study was conducted to examine the diuretic and hypouricemic effects of Orthosiphon stamineus leaf extracts. MATERIALS AND METHODS: The diuretic effect of different methanol extracts was examined by treating different groups of Sprague-Dawley rats with single (2g/kg) oral doses of methanol and methanol:water (1:1) extracts. Hydrochlorothiazide (10mg/kg) was used as positive control in acute study. Methanol and methanol water (1:1) extracts at 0.5 g/kg were administered for a period of 7 consecutive days. Cumulative urine volume and electrolytes (Na+ and K+) concentrations at different time intervals were measured. On the other hand, hypouricemic activity of methanol:water extract (1:1) was experimented using different oral single doses (0.25, 0.5, 1 and 2g/kg). Allopurinol was used as positive control. Uric acid concentration in serum was analyzed by using RP-HPLC at 280 nm. RESULTS: Sodium and potassium excretion increased significantly (p<0.05 and <0.01) in the first 8h of treatment with a single dose (2g/kg) of the extracts in a pattern comparable to that of the known diuretic hydrochlorothiazide. Meanwhile, repeated administration of 0.5 g/kg methanol:water (1:1) extract showed a significant increase in urine volume (from day 3 to day 7) (p<0.01) and electrolytes excretion (Na+ and K+) from day 2 to day 7 (p<0.05 and <0.01). On the other hand, 0.5, 1 and 2g/kg of methanol:water (1:1) extract and the standard allopurinol reduced the serum urate level in hyperuricemic rats at hour 6. CONCLUSION: These results provided an evidence of the high tendency of methanol:water (1:1) extract of Orthosiphon stamineus towards diuretic and hypouricemic effects in rats.

Highly enriched cardiomyocytes from human embryonic stem cells.

BACKGROUND: Current efforts to direct differentiation of human embryonic stem cells (hESC) into a particular cell lineage usually lead to a heterogeneous cell population with only a fraction of the desired cell type present. We show the generation of an essentially pure population of human cardiomyocytes from hESC using lineage selection. METHODS: A construct comprising the murine alpha-myosin heavy chain (alpha-MHC) promoter driving the neomycin-resistance gene was introduced into hES3 cells to generate stable transgenic lines. Transgenic hESC lines were differentiated into cardiomyocytes and subjected to G418 selection. Both G418-selected and non-selected cardiomyocytes were characterized by immunocytochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. The teratoma-forming potential of differentiated cells was assessed by injection of about 2 million cells into the hind limb muscle of SCID mice. Results After cardiac differentiation and antibiotic selection in a suspension culture process, more than 99% of the transgenic cells showed immunoreactivity to alpha-MHC and alpha-actinin; this enrichment efficiency was observed for independent transgenic cell lines. Quantitative RT-PCR analysis revealed high levels of enrichment for cardiac-specific messages in the selected population. Importantly, injection of selected cells into six SCID mice resulted in no apparent teratoma formation, in contrast to differentiated but non-selected controls. DISCUSSION: Our results represent a significant step toward scalable production of pure human cardiomyocytes from stable, expandable hESC lines that will facilitate the development of cell therapies, safety pharmacology and drug discovery.

Decoupling of normal CD40/interleukin-4 immunoglobulin heavy chain switch signal leads to genomic instability in SGH-MM5 and RPMI 8226 multiple myeloma cell lines.

The processes mediating genomic instability and clonal evolution are obscure in multiple myeloma (MM). Acquisition of new chromosomal translocations into the switch region of the immunoglobulin heavy chain (IgH) gene (chromosome 14q32) in MM, often heralds transformation to more aggressive disease. Since the combined effects of CD40 plus interleukin-4 (IL-4) mediate IgH isotype class switch recombination (CSR), and this process involves DNA double strand break repair (DSBR), we hypothesized that CD40 and/or IL-4 activation of MM cells could induce abnormal DNA DSBR and lead to genomic instability and clonal evolution. In this study, we show that MM cell lines that are optimally triggered via CD40 and/or IL-4 demonstrate abnormal decoupling of IL-4 signal transduction from CD40. Specifically, CD40 alone was sufficient to trigger maximal growth of tumor cells. We further demonstrate that CD40 triggering induced both DNA DSBs as well as newly acquired karyotypic abnormalities in MM cell lines. Importantly, these observations were accompanied by induction of activation induced cytidine deaminase expression, but not gross apoptosis. These data support the role of abnormal CD40 signal transduction in mediating genomic instability, suggesting a role for the CD40 pathway and intermediates in myelomagenesis and clonal evolution in vivo.

An acid phosphatase from Manihot glaziovii as an alternative to alkaline Phosphatase for molecular cloning experiments.

An acid phosphatase, free of deoxyribonuclease activity, was isolated from Manihot glaziovii leaves. It had a Mr of 78 kDa and was optimally active at pH 4.3 and 52 degrees C. It was inactivated at 65 degrees C over 15 min. It had a broad substrate specificity with strongest activity towards p-nitrophenyl phosphate. The enzyme dephosphorylated linearized pUC18 DNA and preventing self-ligation under the same conditions used for calf intestine alkaline phosphatase.

Internal fixation of unstable fracture dislocations of the proximal interphalangeal joint.

We report a group of 14 patients with fracture dislocations of the proximal interphalangeal joint with fracture fragments of adequate size to allow reduction of the proximal interphalangeal joint and internal mini screw fixation of the bone fragment attached to the palmar plate to the base of the middle phalanx. Three years after surgery, (range 25-52 months) the average total active range of motion of the proximal interphalangeal joint was 100 degrees (range 65-115 degrees) for the acute group (operation within 14 days of injury, n=7) and 86 degrees (range 60-110 degrees) for the chronic group (operation on average 46 days after injury, range 21-120 days, n=7). Longer delay from injury was associated with a decreased total range of motion (P=0.028). Further subluxation occurred in three chronic group patients, one required further surgery. The key to successful treatment of this injury is the re-establishment of joint congruity and early mobilization. With appropriate patient selection, pain free, satisfactory range of motion can be achieved. There is a risk of persistent subluxation or dislocation, particularly if treatment is delayed.

Molecular descriptors that influence the amount of drugs transfer into human breast milk.

Most drugs are excreted into breast milk to some extent and are bioavailable to the infant. The ability to predict the approximate amount of drug that might be present in milk from the drug structure would be very useful in the clinical setting. The aim of this research was to simplify and upgrade the previously developed model for prediction of the milk to plasma (M/P) concentration ratio, given only the molecular structure of the drug. The set of 123 drug compounds, with experimentally derived M/P values taken from the literature, was used to develop, test and validate a predictive model. Each compound was encoded with 71 calculated molecular structure descriptors, including constitutional descriptors, topological descriptors, molecular connectivity, geometrical descriptors, quantum chemical descriptors, physicochemical descriptors and liquid properties. Genetic algorithm was used to select a subset of the descriptors that best describe the drug transfer into breast milk and artificial neural network (ANN) to correlate selected descriptors with the M/P ratio and develop a QSAR. The averaged literature M/P values were used as the ANN's output and calculated molecular descriptors as the inputs. A nine-descriptor nonlinear computational neural network model has been developed for the estimation of M/P ratio values for a data set of 123 drugs. The model included the percent of oxygen, parachor, density, highest occupied molecular orbital energy (HOMO), topological indices (chiV2, chi2 and chi1) and shape indices (kappa3, kappa2), as the inputs had four hidden neurons and one output neuron. The QSPR that was developed indicates that molecular size (parachor, density) shape (topological shape indices, molecular connectivity indices) and electronic properties (HOMO) are the most important for drug transfer into breast milk. Unlike previously reported models, the QSPR model described here does not require experimentally derived parameters and could potentially provide a useful prediction of M/P ratio of new drugs only from a sketch of their structure and this approach might also be useful for drug information service. Regardless of the model or method used to estimate drug transfer into breast milk, these predictions should only be used to assist in the evaluation of risk, in conjunction with assessment of the infant's response.