Retain rural doctors: Burnout, depression and anxiety in medical doctors working in rural KwaZulu-Natal Province, South Africa.

BACKGROUND: There is a need to retain medical doctors in rural areas to ensure equitable access to healthcare for rural communities. Burnout, depression and anxiety may contribute to difficulty in retaining doctors. Some studies have found high rates of these conditions in medical doctors in general, but there is little research available on their prevalence among those working in the rural areas of South Africa (SA). OBJECTIVES: To determine the prevalence of burnout, depression and anxiety in doctors working in rural district hospitals in northern KwaZulu-Natal (KZN) Province, SA, and to explore the associated sociodemographic and rural work-related factors. METHODS: We performed a quantitative descriptive cross-sectional study in three districts in northern KZN among medical doctors working at 15 rural district hospitals during August and September 2020. The prevalences of burnout, depression and anxiety were measured using the Maslach Burnout Inventory, the Patient Health Questionnaire-9 and the Generalized Anxiety Disorder 7-item questionnaire, respectively. The sociodemographic and rural occupational profiles were assessed using a questionnaire designed by the authors. Descriptive statistics were used to analyse the data. RESULTS: Of 96 doctors who participated in the study, 47.3% (n=44) were aged between 24 and 29 years and 70.8% (n=68) had worked in a rural setting for <5 years. Of the participants, 68.5% (n=61) were considered to have burnout. The screening tests for depression and anxiety were positive for 35.6% (n=31) and 23.3% (n=20) of participants, respectively. Burnout alone was significantly associated with female gender (84.8%; n=39) (χ2=11.65, df=1, p=0.01). Burnout (χ2=8.14, df=3, p=0.04) and anxiety (χ2=12.96, df=3, p<0.01) were both significantly associated with occupational rank, with 85.2% (n=23) of community service medical officers (CSMOs) reporting the former and 29.6% (n=8) screening positive for generalised anxiety disorder. Burnout (χ2=7.61, df=1, p=0.01), depression (χ2=5.49, df=1, p=0.02) and anxiety (χ2=4.08, df=1, p=0.04) were all shown to be significantly associated with doctors planning to leave the public sector in the next 2 years. CONCLUSIONS: Our study found high rates of burnout, depression and anxiety in rural doctors in northern KZN, all of which were associated with the intention to leave the public sector in the next 2 years. Of particular concern was that CSMOs as a group had high burnout and anxiety rates and female gender was associated with burnout. We recommend that evidence-based solutions are urgently implemented to prevent burnout and retain rural doctors.

Difference in the antibacterial action of epigallocatechin gallate and theaflavin 3,3'-di-O-gallate on Bacillus coagulans.

AIMS: To study the mechanism of the antibacterial action of tea polyphenols such as catechins and theaflavins against Bacillus coagulans, and the interaction of epigallocatechin gallate (EGCg) or theaflavin 3,3'-di-O-gallate (TFDG) with the surface of B. coagulans cells was investigated. METHODS AND RESULTS: The antibacterial activities of EGCg and TFDG against B. coagulans cells were measured by counting of the viable cells after the mixing with each polyphenol. Bactericidal effect of TFDG was shown at the concentration of greater than or equal to 62·5 mg l-1 ; however, at the same concentration, EGCg did not. According to the results of two dimensional (2D)-electrophoresis analysis, TFDG seemed to interact with cytoplasmic membrane proteins. The activity of the glucose transporters of the cells decreased 40% following the treatment with TFDG of 62·5 mg l-1 ; however, this decrease was only slight in case of EGCg. This result was in accordance with the strength of their bactericidal activities. CONCLUSION: Our results suggest that the direct interaction between membrane proteins and TFDG is an important factor in the antibacterial activity of polymerized catechins, affecting their functions and leading to cell death. SIGNIFICANCE AND IMPACT OF THE STUDY: Tea polyphenols can effectively use the prevention of product spoilage in the food and beverage industry.

Development of canine X-chromosome inactivation pattern analysis for the detection of cell clonality by incorporating the examination of the SLIT and NTRK-like family member 4 (SLITRK4) gene.

X-chromosome inactivation pattern (XCIP) analysis can be used to assess the clonality of cell populations of various origin by distinguishing the methylated X chromosome from the unmethylated X chromosome. In this study, the utility of XCIP analysis was improved by incorporating the examination of AC dinucleotide repeats in SLIT and NTRK-like family member 4 (SLITRK4) gene into the previously reported CAG repeat examination of androgen receptor (AR) gene in dogs. The rate of heterozygosity when both genes were analysed (125/150, 83.3%) was higher than AR gene examination alone (86/150, 57.3%). Blood samples from heterozygous dogs in either AC-1 or AC-2 of SLITRK4 gene were examined for the corrected inactivation allele ratio (CIAR), resulting in the determination of a reference range of CIAR <3.8 in non-neoplastic cell/tissue samples. Using this analytical method, 49% (21/43) of neoplastic tissue samples from dogs showed a CIAR >3.8, indicating the presence of a clonal population. Through the present study, the availability of canine XCIP analysis was improved by incorporating the examination of the SLITRK4 gene, providing a highly useful laboratory examination system for the detection of the clonality of various cell/tissue samples in dogs.

Identification of patients with recent-onset psychosis in KwaZulu Natal, South Africa: a pilot study with traditional health practitioners and diagnostic instruments.

PURPOSE: There is considerable variation in epidemiology and clinical course of psychotic disorders across social and geographical contexts. To date, very little data are available from low- and middle-income countries. In sub-Saharan Africa, most people with psychoses remain undetected and untreated, partly due to lack of formal health care services. This study in rural South Africa aimed to investigate if it is possible to identify individuals with recent-onset psychosis in collaboration with traditional health practitioners (THPs). METHODS: We developed a strategy to engage with THPs. Fifty THPs agreed to collaborate and were asked to refer help-seeking clients with recent-onset psychosis to the study. At referral, the THPs rated probability of psychosis ("maybe disturbed" or "disturbed"). A two-step diagnostic procedure was conducted, including the self-report Community Assessment of Psychic Experiences (CAPE) as screening instrument, and a semi-structured interview using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN). Accuracy of THP referrals, and test characteristics of the THP rating and the CAPE were calculated. RESULTS: 149 help-seeking clients were referred by THPs, of which 44 (29.5%) received a SCAN DSM-IV diagnosis of psychotic disorder. The positive predictive value of a THP "disturbed" rating was 53.8%. Test characteristics of the CAPE were poor. CONCLUSION: THPs were open to identifying and referring individuals with possible psychosis. They recognized "being disturbed" as a condition for which collaboration with formal psychiatric services might be beneficial. By contrast, the CAPE performed poorly as a screening instrument. Collaboration with THPs is a promising approach to improve detection of individuals with recent-onset psychosis in rural South Africa.

A retrospective cohort study investigating risk factors for the failure of Thoroughbred racehorses to return to racing after superficial digital flexor tendon injury.

A retrospective cohort study was conducted to investigate risk factors for the failure of Thoroughbred racehorses to return to racing after an injury of the superficial digital flexor tendon (SDFT). Successful return was defined as the completion of five or more races after SDFT injury. The official Japan Racing Association (JRA) medical records of racehorses with a core-type SDFT injury were reviewed for clinical variables related to the characteristics of the horse and the severity of SDFT injuries at the time of diagnosis. Data on racing outcomes were obtained from the official JRA racing database. Risk factors were screened using univariable logistic regression and subsequent multivariable model building. Forty-nine of 346 (14.2%) horses successfully returned to racing after SDFT injuries. Multivariable model building revealed that an increase in the total number of injured zones (defined as the total number of zones in which the injured hypoechoic area was observed at the time of ultrasonographic diagnosis of SDFT injury) was associated with an increased risk of failure to return to racing after SDFT injury. Horse characteristics, such as age, body mass and sex, were not associated with a successful return to racing. In the rehabilitation of cases with larger (longer) lesions, more effective and careful medical management may be needed for an improvement in the athletic outcomes.

Intimate partner violence among HIV-serodiscordant couples in Durban, South Africa.

BACKGROUND: South Africa (SA) has a high prevalence rate of intimate partner violence (IPV) and HIV, both of which can be exacerbated further by HIV serodiscordancy in the couple dyad. Further exploration of the discordancy sidedness in known mediating factors, such as alcohol abuse risk and post-traumatic stress (PTS), is required. OBJECTIVES: To investigate the extent of and gender differences in IPV, alcohol abuse risk and PTS symptoms among HIV-serodiscordant couples in Durban, SA, and to analyse these further with regard to female HIV serostatus. METHODS: A cross-sectional analysis of data on 30 serodiscordant couples was conducted at the point of enrolment into a pilot study of an HIV risk reduction intervention. The statistical procedure for a dependent small sample was applied to examine gender differences in IPV, alcohol use and PTS symptoms among HIV-serodiscordant couples. RESULTS: The woman was HIV-positive in 18 (60.0%) of the 30 serodiscordant couples enrolled. Exposure to IPV differed significantly between men (28.6%) and women (89.3%) (proportional difference -0.61, 95% confidence interval (CI) -0.82 - -0.39). The Wilcoxon signed-rank test showed that PTS symptom scores differed significantly between men (median 22, interquartile range (IQR) 23) and women (median 44, IQR 28) (p=0.03). When the above analysis was stratified by female HIV serostatus, significant gender differences were found in IPV and PTS in the couples where the woman was HIV-positive. There were no significant gender differences for alcohol abuse risk. CONCLUSIONS: The findings demonstrated high levels of IPV in HIV-serodiscordant couples and a significant gender difference in mental health risk such as PTS in such relationships, particularly where the woman was HIV-positive. HIV intervention programmes should address gender-based violence and inequity among heterosexual couples.

Vastus intermedius vs vastus lateralis fascicle behaviors during maximal concentric and eccentric contractions.

Vastus intermedius (VI) plays a major role in knee extension, but its fascicle behaviors during dynamic contractions are not well understood. This study aimed to compare VI and vastus lateralis (VL) fascicle behaviors during singular maximal concentric and eccentric contractions. Thirteen men (27.1 ± 3.4 years) performed maximal isokinetic concentric contractions through knee joint angles of 105° to 35° (0° = full extension) and eccentric contractions from 35° to 105° at an angular velocity of 30°/s. Longitudinal VI and VL sonographic images were simultaneously recorded at 30 Hz, and muscle fascicle lengths at the knee joint angles of 40° and 100° were measured to compare the magnitudes of fascicle length change between the muscles. During concentric contractions, VI and VL fascicle lengths at 100° were 108 ± 12 mm and 104 ± 12 mm, respectively, and shortened by 36 ± 12 mm for VI and 28 ± 13 mm for VL (not statistically different; P = .13) at 40°. During eccentric contractions, VI and VL fascicle lengths at 40° were 72 ± 7 mm and 75 ± 8 mm, respectively, but lengthened by 35 ± 9 mm for VI and 24 ± 5 mm for VL at 100°, with a significant difference between the muscles (P = .01). These results indicate that VI fascicles are lengthened 1.4 times more than VL fascicles during eccentric contractions, whereas VI and VL fascicles shorten similarly during concentric contractions. This suggests a possibility that a greater mechanical strain is imposed to VI than VL during eccentric contractions.

Development and analysis of patient-derived xenograft mouse models in intravascular large B-cell lymphoma.

Intravascular large B-cell lymphoma (IVLBCL) is a distinct disease entity with the peculiar characteristic that tumor cells proliferate within vessels. Despite recent advances in understanding the disease from clinical aspects, the underlying pathogenesis remains unknown. Here we demonstrate analyses of IVLBCL biology using four xenograft mouse models established from primary IVLBCL samples. In all four models, the main characteristic of IVLBCL tumor cell proliferation within vessels was retained. Time-lapse engraftment analyses revealed that the tumor cells initially engrafted and proliferated in the sinusoids and vessels in the liver and then engrafted and proliferated in multiple organs. Intriguingly, serial passage of tumor cells from the adrenal gland of a transplanted mouse developed from primary patient bone marrow cells into a second mouse showed that the tumor cells mainly distributed into the adrenal gland in the second mouse, implying the existence of clonal selection and/or evolution at engraftment of a specific organ. Gene expression profiling analyses demonstrated that the gene set associated with cell migration was enriched for normal peripheral blood B cells, indicating that inhibition of cell migration might be involved in IVLBCL pathogenesis. In conclusion, the mouse xenograft models described here are essential tools for uncovering IVLBCL biology.

Revisiting the supratrigeminal nucleus in the rat.

The supratrigeminal nucleus (Vsup), originally proposed as a premotoneuron pool in the trigeminal reflex arc, is a key structure of jaw movement control. Surprisingly, however, the location of the rat Vsup has not precisely been defined. In light of our previous cat studies, we made two hypotheses regarding the rat Vsup: (1) the Vsup is cytoarchitectonically distinguishable from its surrounding structures; (2) the Vsup receives central axon terminals of the trigeminal mesencephalic nucleus (Vmes) neurons which are primary afferents innervating muscle spindles of jaw-closing muscles and periodontal ligaments around the teeth. To test the first hypothesis, we examined the cytoarchitecture of the rat Vsup. The Vsup was identified as an area medially adjacent to the dorsomedial part of trigeminal principal sensory nucleus (Vp), and extended from the level just rostral to the caudal two-thirds of the trigeminal motor nucleus (Vmo) to the level approximately 150 µm caudal to the Vmo. Our rat Vsup was much smaller and its location was considerably different in comparison to the Vsup reported previously. To evaluate the second hypothesis, we tested the distribution patterns of Vmes primary afferent terminals in the cytoarchitectonically identified Vsup. After transganglionic tracer applications to the masseter, deep temporal, and medial pterygoid nerves, a large number of axon terminals were observed in all parts of Vsup (especially in its medial part). After applications to the inferior alveolar, infraorbital, and lingual nerves, a small number of axon terminals were labeled in the caudolateral Vsup. The Vsup could also be identified electrophysiologically. After electrical stimulation of the masseter nerve, evoked potentials with slow negative component were isolated only in the Vsup. The present findings suggest that the rat Vsup can be cytoarchitectonically and electrophysiologically identified, receives somatotopic termination of the trigeminal primary afferents, and principally receives strong termination of the spindle Vmes primary afferents.

Jaw movement-related primary somatosensory cortical area in the rat.

It has anatomically been revealed that the rostral part of the rat primary somatosensory cortex (S1) directly projects to the dorsal part of the trigeminal oral subnucleus (dorVo) and the dorsal part of juxtatrigeminal region (dorVjuxt), and that the dorVo and dorVjuxt contain premotoneurons projecting directly to the jaw-opening or jaw-closing motoneurons in the trigeminal motor nucleus (Vmo). However, little is known about how the rostral S1 regulates jaw movements in relation to its corticofugal projections. To address this issue, we performed intracortical microstimulation of the rat rostral S1 by monitoring jaw movements and electromyographic (EMG) activities. We for the first time found that low-frequency long-train stimulation of the rostral S1 induced single sustained opening of the jaw with elevated EMG activities of the anterior digastric muscles (jaw-opener). The effective sites for the low-frequency long-train stimulation overlapped the S1 sites where traditional high-frequency short-train stimulation was effective to induce single twitch-like jaw movement. We also found that the effective sites for the two kinds of train stimuli were included in the rostral S1 area, which has previously been identified to send direct projections to the dorVo or the dorVjuxt. Specifically, the most effective stimulation sites for the two kinds of train stimuli were located in the rostralmost part of S1 which has been reported to emanate strong direct projections to the dorVjuxt but less to the dorVo. Therefore, the present study suggests that the rat rostral S1, especially its rostralmost part, plays an important role in controlling jaw movements by activation of direct descending projections from the rostral S1 to the trigeminal premotoneuron pools, especially to the dorVjuxt.

Somatotopic direct projections from orofacial areas of primary somatosensory cortex to pons and medulla, especially to trigeminal sensory nuclear complex, in rats.

The primary somatosensory cortex (S1) projects to the thalamus and brainstem somatosensory nuclei and modulates somatosensory information ascending to the S1 itself. However, the projections from the S1 to the brainstem second-order somatosensory neuron pools have not been fully studied. To address this in rats, we first revealed the somatotopic representation of orofacial areas in the S1 by recording cortical surface potentials evoked by stimulation of the lingual, mental, infraorbital, and frontal nerves. We then examined the morphology of descending projections from the electrophysiologically defined orofacial S1 areas to the pons and medulla after injections of an anterograde tracer, biotinylated dextranamine (BDA), into the orofacial S1 areas. BDA-labeled axon terminals were seen mostly in the trigeminal sensory nuclear complex (TSNC) and had a strong contralateral predominance. They also showed a somatotopic arrangement in dorsoventral and superficial-deep directions within almost all rostrocaudal TSNC levels, and in a rostrocaudal direction within the trigeminal caudal subnucleus. In the principal nucleus (Vp) or oral subnucleus (Vo) of TSNC, the BDA-labeled axon terminals showed a somatotopic arrangement closely matched to that of the electrophysiologically defined projection sites of orofacial primary afferents; these projection sites were marked by injections of a retrograde tracer, Fluorogold (FG), into the Vp or Vo. The FG injections labeled a large number of S1 neurons, with a strong contralateral predominance, in a somatotopic manner, which corresponded to that presented in the electrophysiologically defined orofacial S1 areas. The present results suggest that the orofacial S1 projections to somatotopically matched regions of trigeminal second-order somatosensory neuron pools may allow the orofacial S1 to accurately modulate orofacial somatosensory transmission to higher brain centers including the orofacial S1 itself.

Afterpulse-like phenomenon of superconducting single photon detector in high speed quantum key distribution system.

We discuss our estimates of the performance of a superconducting single photon detector (SSPD) in a high speed quantum key distribution (QKD) system. We find that at high repetition operation reflections from the readout circuit at room temperature causes an afterpulse-like phenomenon, and drastically increases the quantum bit error rate (QBER). Such effects are not seen during low frequency operation. By using an amplifier with a small reflection coefficient S11, we succeed in reducing the afterpulse-like phenomenon and increasing a secure key rate.

Efficient and low-noise single-photon avalanche photodiode for 1.244-GHz clocked quantum key distribution.

An efficient and low-noise 1.244-GHz gating InGaAs single-photon avalanche photodiode (SAPD) was developed for a high-speed quantum key distribution (QKD) system. An afterpulsing probability of 0.61% and a dark count probability per gate of 0.71 ×10-6 were obtained at a detection efficiency of 10.9% for 1.55-µm photons. Furthermore, our SAPD successfully coped with high detection efficiency (≤ 25%) and quite low afterpulsing noise (≤ 3% for ≤ 25% efficiency) at the same time. Its potential was verified using the actual QKD setups installed over a metropolitan area network.

Potential role for S100A4 in the disruption of the blood-brain barrier in collagen-induced arthritic mice, an animal model of rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease associated with chronic inflammation of the joints. RA has been shown to increase the morbidity of and mortality due to cardiovascular and cerebrovascular diseases. We recently reported that cerebrovascular permeability was increased in mice with collagen-induced arthritis (CIA), an animal model of RA. S100A4, a member of the S100 family, is up-regulated in synovial fluid and plasma from RA patients. This study was aimed at evaluating a role of S100A4 in the mediation of blood-brain barrier (BBB) dysfunction in CIA mice. CIA was induced by immunization with type II collagen in mice. Cerebrovascular permeability was assessed by measurement of sodium fluorescein (Na-F) levels in the brains of control and CIA mice. Serum S100A4 concentrations in control and CIA mice were measured by enzyme-linked immunosorbent assays (ELISA). Accumulation of Na-F in the brain and serum levels of S100A4 were increased in CIA mice. Increased S100A4 levels in the serum are closely correlated with hyperpermeability of the cerebrovascular endothelium to Na-F. We investigated whether S100A4 induces BBB dysfunction using mouse brain capillary endothelial cells (MBECs). S100A4 decreased the transendothelial electrical resistance and increased Na-F permeability in the MBECs. S100A4 reduced the expression of occludin, a tight junction protein, and stimulated p53 expression in MBECs. These findings suggest that S100A4 increases paracellular permeability of MBECs by decreasing expression levels of occludin, at least in part, via p53. The present study highlights a potential role for S100A4 in BBB dysfunction underlying cerebrovascular diseases in patients with RA.

Field test of quantum key distribution in the Tokyo QKD Network.

A secure communication network with quantum key distribution in a metropolitan area is reported. Six different QKD systems are integrated into a mesh-type network. GHz-clocked QKD links enable us to demonstrate the world-first secure TV conferencing over a distance of 45km. The network includes a commercial QKD product for long-term stable operation, and application interface to secure mobile phones. Detection of an eavesdropper, rerouting into a secure path, and key relay via trusted nodes are demonstrated in this network.

Optimisation of bone marrow aspiration from the equine sternum for the safe recovery of mesenchymal stem cells.

REASONS FOR PERFORMING STUDY: Mesenchymal stem cell (MSC) therapy for orthopaedic disease is being used with increasing frequency; there is a need to define a safe, reliable and effective technique for the recovery of MSCs from the sternum of the horse. OBJECTIVES: To describe an optimised safe technique for obtaining bone marrow-derived MSCs from the sternum of the Thoroughbred horse. METHODS: The anatomical relationship of the sternum with the heart and internal anatomy was demonstrated in cadavers. Sternal anatomy was evaluated ultrasonographically and after midline sectioning. Sternebrae were examined histologically after aspiration to determine the effect of needle insertion. The quality of the aspirate was evaluated as the number of colony-forming units from sequential and separately aspirated 5 ml aliquots and assessed for their multipotency using trilineage differentiation. RESULTS: The optimal safe location for the needle was the 5th sternebra because it had a safe dorsoventral thickness and was cranial to the apex of the heart. This sternebra could be reliably identified ultrasonographically. Aspirates could also be obtained from the 4th and 6th sternebrae, although the former is between the front limbs and the latter closer to the heart. Minimal disruption of the internal bony architecture was seen after needle insertion through the thin outer cortex and the first 5 ml aliquot contained the greatest number of colony-forming units of mesenchymal stem cells with trilineage capabilities. CONCLUSIONS: Accurate placement of a Jamshidi needle into the medullary cavity of the 4th-6th individual sternebrae is facilitated by the use of ultrasonography and enables aspiration of bone marrow reliably with minimal damage to the sternum and risk to the horse. POTENTIAL CLINICAL RELEVANCE: Sternal marrow aspiration as described is a safe and reliable technique to obtain MSCs for orthopaedic cell-based therapies.

100 ps time-resolved solution scattering utilizing a wide-bandwidth X-ray beam from multilayer optics.

100 ps time-resolved X-ray solution-scattering capabilities have been developed using multilayer optics at the beamline NW14A, Photon Factory Advanced Ring, KEK. X-ray pulses with an energy bandwidth of DeltaE/E = 1-5% are generated by reflecting X-ray pulses (DeltaE/E = 15%) through multilayer optics, made of W/B(4)C or depth-graded Ru/C on silicon substrate. This tailor-made wide-bandwidth X-ray pulse provides high-quality solution-scattering data for obtaining photo-induced molecular reaction dynamics. The time-resolved solution scattering of CH(2)I(2) in methanol is demonstrated as a typical example.

The advantage of using carbon nanotubes compared with edge plane pyrolytic graphite as an electrode material for oxidase-based biosensors.

Carbon nanotubes (CNTs) are promising materials for use in amperometric biosensors. The defect sites at their ends, and on their sidewalls, are considered to be edge plane-like defects and show high electrocatalytic activity toward several biological molecules. However, electrocatalytic activity toward H(2)O(2) has not been compared among bamboo-structured CNTs (BCNTs), which have many defect sites; hollow-structured CNTs (HCNTs), which have few defect sites; edge plane pyrolytic graphite (EPG); and traditional glassy carbon (GC). The advantages of using CNTs in electrodes for biosensors are still equivocal. To confirm the utility of CNTs, we analyzed the electrochemical performance of these four carbon electrodes. The slope of the calibration curve for H(2)O(2) at potentials of both +0.6 V and -0.1 V obtained with a BCNT paste electrode (BCNTPE) was more than 10 times greater than the slopes obtained with an HCNT paste electrode and a GC electrode, reflecting the BCNT's larger number of defect sites. Although the slope with the EPG electrode (EPGE) was about 40 times greater than that with BCNTPE at +0.6 V, the slopes with these two carbon electrodes were nearly equivalent at -0.1 V. EPGE demonstrated excessive electrochemical activity, detecting currents on the basis of consumption of oxygen and oxidation of ascorbic acid, even at -0.1 V. In contrast, BCNTPE could dominantly detect a cathodic current for H(2)O(2) at -0.1 V, even when interfering molecules were added. BCNTPE possesses appropriate electrochemical activity and is an effective electrode materials for developing interference-free oxidase-based biosensors operated by the application of an appropriate potential.