Mapping human serum induced gene networks as a basis for the creation of biomimetic periosteum for bone repair

The periosteum is a highly vascularised, collagen-rich tissue that plays a crucial role in directing bone repair. This is orchestrated primarily by its resident progenitor cell population. Indeed, preservation of periosteum integrity is critical for bone healing. Cells extracted from the periosteum retain their osteochondrogenic properties and as such are a promising basis for tissue engineering strategies for the repair of bone defects. However, the culture expansion conditions, and the way in which the cells are reintroduced to the defect site are critical aspects of successful translation. Indeed, expansion in human serum and implantation on biomimetic materials has previously been shown to improve in vivo bone formation. As such, this study aimed to develop a protocol to allow for the expansion of human periosteum derived cells (hPDCs) in a biomimetic periosteal-like environment. The expansion conditions were defined through the investigation of the bioactive cues involved in augmenting hPDC proliferative and multipotency characteristics, based on transcriptomic analysis of cells cultured in human serum. Master regulators of transcriptional networks were identified and an optimised periosteal derived-growth factor cocktail (PD-GFC; containing β-Estradiol, FGF2, TNFα, TGFβ, IGF-1 and PDGF-BB) was generated. Expansion of hPDCs in PD-GFC resulted in serum mimicry with regards to the cell morphology, proliferative capacity and chondrogenic differentiation. When incorporated into a 3D collagen-type-1 matrix and cultured in PD-GFC, the hPDCs migrated to the surface that represented the matrix topography of the periosteum cambium layer. Furthermore, gene expression analysis revealed a downregulated Wnt and TGFβ signature and an upregulation of CREB, which may indicate the hPDCs are recreating their progenitor cell signature. This study highlights the first stage in the development of a biomimetic periosteum which may have applications in bone repair

The sensitivity to change of the cluster headache quality of life scale assessed before and after deep brain stimulation of the ventral tegmental area.

BACKGROUND: Cluster headache (CH) is a trigeminal autonomic cephalalgia (TAC) characterized by a highly disabling headache that negatively impacts quality of life and causes limitations in daily functioning as well as social functioning and family life. Since specific measures to assess the quality of life (QoL) in TACs are lacking, we recently developed and validated the cluster headache quality of life scale (CH-QoL). The sensitivity of CH-QoL to change after a medical intervention has not been evaluated yet. METHODS: This study aimed to test the sensitivity to change of the CH-QoL in CH. Specifically we aimed to (i) assess the sensitivity of CH-QoL to change before and following deep brain stimulation of the ventral tegmental area (VTA-DBS), (ii) evaluate the relationship of changes on CH-QoL with changes in other generic measures of quality of life, as well as indices of mood and pain. Ten consecutive CH patients completed the CH-QoL and underwent neuropsychological assessment before and after VTA-DBS. The patients were evaluated on headache frequency, severity, and load (HAL) as well as on tests of generic quality of life (Short Form-36 (SF-36)), mood (Beck Depression Inventory, Hospital Anxiety and Depression Rating Scale), and pain (McGill Pain Questionnaire, Headache Impact Test, Pain Behaviour Checklist). RESULTS: The CH-QoL total score was significantly reduced after compared to before VTA-DBS. Changes in the CH-QoL total score correlated significantly and negatively with changes in HAL, the SF-36, and positively and significantly with depression and the evaluative domain on the McGill Pain Questionnaire. CONCLUSIONS: Our findings demonstrate that changes after VTA-DBS in CH-QoL total scores are associated with the reduction of frequency, duration, and severity of headache attacks after surgery. Moreover, post VTA-DBS improvement in CH-QoL scores is associated with an amelioration in quality of life assessed with generic measures, a reduction of depressive symptoms, and evaluative pain experience after VTA-DBS. These results support the sensitivity to change of the CH-QoL and further demonstrate the validity and applicability of CH-QoL as a disease specific measure of quality of life for CH

Behind the counter: pharmacies and dispensing patterns of pharmacy attendants in Karachi.

BACKGROUND: There is little literature available on dispensing patterns and unsupervised sale of medicines from pharmacies in developing countries. OBJECTIVE: This study obtained background information on pharmacies assessed the level of training, knowledge and dispensing patterns of pharmacy attendants in Karachi. METHODOLOGY: This is a descriptive cross sectional study with convenient sampling. A structured questionnaire was used to interview pharmacy attendants. RESULTS: Of the 219 pharmacies surveyed, 62% reported more than 50 customers daily and 20% also sold items of general provision. Mean operating hours were 13. Only 24 (11%) had a visible license. On an average 3 attendants were employed per pharmacy. We interviewed one in each. Amongst the 219 interviewed, 77 (35%) were intermediate qualified and only 26 (12%) pharmacologically trained. Correct frequency of ORS administration was not known by 167 (76%) and 21% incorrectly suggested an anti-diarrhoeal preparation for viral diarrhoea in children. The knowledge of those with pharmacological training was significantly better. For respiratory tract infection in children approximately 60% did not know the correct dose of Paracetamol and Amoxicillin. Only 13 (6%) knew that Propanalol was contraindicated in hypertensive asthamatics. For Cotrimoxazole, metronidazole and lomotil only 40%, 21% and 15% respectively, were aware that these could not be dispensed without prescription. CONCLUSION: In the absence of trained pharmacists existing pharmacy attendants should be trained to improve drug-dispensing patterns

THE NEXUS between TRADE LIBERALIZATION and POVERTY: A DISAGGREGATED ANALYSIS

Decades after trade liberalization, poverty among the developing countries has continued to rise as their economies adjust to fierce and increasing external competition. This study investigates the impact of the 1988 trade reforms on poverty in Pakistan using micro-level data from 1990 to 2005. Using the feasible generalized least squares (FGLS) model in panel setting to address the problem of heteroskedasticity, we explored the impact of trade liberalization on the poverty level in Pakistan. The findings reveal that reductions in import tariffs have increased Pakistan s level of poverty. Our findings are robust and impervious to different poverty measures (i.e., headcount ratio, poverty gap, and squared poverty gap). Also, it was observed that lagged trade policies are associated with poverty in Pakistan. The rise in poverty may be attributed to the lower participation of the poor in external markets. It is recommended that policymakers enact policies that will encourage poor people to participate in external markets if they wish to benefit from trade liberalization. © 2022 AESS Publications. All Rights Reserved

Evaluating the utility of inflammatory markers in the diagnosis of soft tissue abscesses of the forearm and hand

Upper extremity abscesses frequently present to the acute care setting with inconclusive physical examination and imaging findings. We sought to investigate the diagnostic accuracy of inflammatory markers including white blood cell (WBC) count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). A retrospective cohort study was performed to identify subjects ≥18 years treated with surgical debridement of upper extremity abscesses at our institution between January 2012 and December 2015. In this study, 188 patients were screened, and 72 met the inclusion criteria. A confirmed abscess as defined by culture positivity was present in 67 (93.1 %) cases. The sensitivity of WBC, ESR, or CRP individually was 0.45, 0.71, and 0.81. The specificity of WBC, ESR, or CRP individually was 0.80, 0.80, and 0.40. In combination all three markers when positive had a sensitivity of 0.26 and specificity of 1.0. These values were similar among patients with diabetes and those with obesity. With the highest sensitivity and lowest specificity, CRP exhibited the most utility as a screening test (level IV).</p

OSTα deficiency: A disorder with cholestasis, liver fibrosis and congenital diarrhea

Solute carrier family 51 alpha subunit (SLC51A ) encodes the alpha subunit of the heteromeric organic solute transporter alpha–beta (OSTα–OSTβ), an important contributor to intestinal bile acid (BA) reabsorption in the enterohepatic circulation.1, 2 Here, we identified the first case of OSTα deficiency in a child with unexplained elevated liver transaminases, cholestasis, and congenital diarrhea

An occasional diagnosis of myasthenia gravis - a focus on thymus during cardiac surgery: a case report

<p>Abstract</p> <p>Background</p> <p>Myasthenia gravis, an uncommon autoimmune syndrome, is commonly associated with thymus abnormalities. Thymomatous myasthenia gravis is considered to have worst prognosis and thymectomy can reverse symptoms if precociously performed.</p> <p>Case report</p> <p>We describe a case of a patient who underwent mitral valve repair and was found to have an occasional thymomatous mass during the surgery. A total thymectomy was performed concomitantly to the mitral valve repair.</p> <p>Conclusion</p> <p>The diagnosis of thymomatous myasthenia gravis was confirmed postoperatively. Following the surgery this patient was strictly monitored and at 1-year follow-up a complete stable remission had been successfully achieved.</p

Vertical transport and electroluminescence in InAs/GaSb/InAs structures: GaSb thickness and hydrostatic pressure studies

We have measured the current-voltage (I-V) of type II InAs/GaSb/InAs double heterojunctions (DHETs) with 'GaAs like' interface bonding and GaSb thickness between 0-1200 \AA. A negative differential resistance (NDR) is observed for all DHETs with GaSb thickness $>$ 60 \AA below which a dramatic change in the shape of the I-V and a marked hysteresis is observed. The temperature dependence of the I-V is found to be very strong below this critical GaSb thickness. The I-V characteristics of selected DHETs are also presented under hydrostatic pressures up to 11 kbar. Finally, a mid infra-red electroluminescence is observed at 1 bar with a threshold at the NDR valley bias. The band profile calculations presented in the analysis are markedly different to those given in the literature, and arise due to the positive charge that it is argued will build up in the GaSb layer under bias. We conclude that the dominant conduction mechanism in DHETs is most likely to arise out of an inelastic electron-heavy-hole interaction similar to that observed in single heterojunctions (SHETs) with 'GaAs like' interface bonding, and not out of resonant electron-light-hole tunnelling as proposed by Yu et al. A Zener tunnelling mechanism is shown to contribute to the background current beyond NDR.Comment: 8 pages 12 fig

1281O Atezolizumab (atezo) vs platinum-based chemo in blood-based tumour mutational burden-positive (bTMB+) patients (pts) with first-line (1L) advanced/metastatic (m)NSCLC: Results of the Blood First Assay Screening Trial (BFAST) phase III cohort C

Background: TMB is a promising biomarker for immunotherapy in NSCLC, but current data are mostly retrospective. As not all pts may have sufficient tissue for comprehensive biomarker testing, bTMB was prospectively tested as a novel biomarker using targeted next-generation sequencing. BFAST (NCT03178552), a global, open-label, multi-cohort trial, evaluated safety and efficacy of targeted therapies or immunotherapy in biomarker-selected pts with unresectable mNSCLC. Here we present results from Cohort C of 1L atezo vs platinum-based chemo in pts with bTMB+ mNSCLC. Methods: We planned to randomise ≈440 pts with 1L mNSCLC with measurable disease per RECIST 1.1 and bTMB ≥10 (9.1 mut/Mb; FMI bTMB assay) 1:1 to atezo 1200 mg IV every 3 weeks or chemo and stratified by tissue availability, ECOG PS, bTMB and histology. The primary endpoint was INV-PFS per RECIST 1.1 in bTMB ≥16 (14.5 mut/Mb) pts. Key secondary endpoints included OS in bTMB ≥10 (intent to treat, ITT) and bTMB ≥16 pts, and INV-PFS in ITT pts. Results: 471 pts were assigned to atezo (n=234) or chemo (n=237). At baseline, 72% had non-squamous histology, 2% never smoked and median SLD was 103 mm. 145 pts with bTMB ≥16 were assigned to atezo and 146 to chemo. At data cutoff (21 May 2020) minimum follow up was 6 mo. INV-PFS difference in bTMB ≥16 pts for atezo vs chemo was not significant (P=0.053; Table). Grade 3-4 TRAEs occurred in 18% (atezo) vs 46% (chemo) of pts. Serious TRAEs occurred in 12% (atezo) vs 14% (chemo). Results at other bTMB thresholds and by F1L CDx will also be presented as an exploratory analysis. Conclusions: The primary PFS endpoint in bTMB ≥16 pts was not met. OS was numerically better with atezo vs chemo but the difference was not statistically significant. The safety profile of atezo vs chemo was favourable and consistent with atezo monotherapy across indications

A global view on star formation: The GLOSTAR Galactic plane survey. VII. Supernova remnants in the Galactic longitude range 28∘<l<36∘28^\circ<l<36^\circ

Context. While over 1000 supernova remnants (SNRs) are estimated to exist in the Milky Way, only less than 400 have been found to date. In the context of this apparent deficiency, more than 150 SNR candidates were recently identified in the D-configuration Very Large Array (VLA-D) continuum images of the 4--8 GHz global view on star formation (GLOSTAR) survey, in the Galactic longitude range $-2^\circ<l<60^\circ$. Aims. We attempt to find evidence of nonthermal synchrotron emission from 35 SNR candidates in the region of Galactic longitude range $28^\circ<l<36^\circ$, and also to study the radio continuum emission from the previously confirmed SNRs in this region. Methods. Using the short-spacing corrected GLOSTAR VLA-D+Effelsberg images, we measure ${\sim}6$ GHz total and linearly polarized flux densities of the SNR candidates and the SNRs that were previously confirmed. We also attempt to determine the spectral indices by measuring flux densities from complementary Galactic plane surveys and from the temperature-temperature plots of the GLOSTAR-Effelsberg images. Results. We provide evidence of nonthermal emission from four candidates that have spectral indices and polarization consistent with a SNR origin, and, considering their morphology, we are confident that three of these (G28.36+0.21, G28.78-0.44, and G29.38+0.10) are indeed SNRs. However, about $25\%$ of the candidates have spectral index measurements that indicate thermal emission, and the rest of them are too faint to have a good constraint on the spectral index yet. Conclusions. Additional observations at longer wavelengths and higher sensitivities will shed more light on the nature of these candidates. A simple Monte-Carlo simulation reiterates the view that future studies must persist with the current strategy of searching for SNRs with small angular size to solve the problem of the Milky Way's missing SNRs.Comment: To be published in A&A. 21 pages, 15 figure