Supplementary Tests Research Articles

Exploring the impact of health worker strikes on maternal and child health in a Kenyan county

BackgroundStudies of the impact of health care workers’ strikes tend to look at facility-level activity rather than populations, with evidence from low and middle-income countries relatively sparse. This study explored the effect of national strikes on maternal and child health. It looked at the impact on health system activity in both public and non-public sectors (e.g. private, faith-based), on health promotion investments like immunisation, and on disease detection like post-partum haemorrhage (PPH). A 100 day doctors’ strike started in December 2016, a 150 day nurses strike from June 2017 and then the clinical officers for 21 days that September.MethodsTime series descriptive analysis of attendance data from the Kenyan Health Management Information System (public, non-public sector facilities). The setting was Kilifi, a coastal county in Kenya with a population of about 1.5 million.ResultsAlong the care pathway from antenatal, postnatal and out-patient child health clinics, activity levels dropped markedly in the public sector with only partial compensatory increases in non-public sector activity. The number of fully immunised children fell during the nurses strike as did women seen with PPH during all strikes. These health care strikes caused significant adverse health impacts at the time and potentially inter-generationally as exemplified by the fall in antenatal haematinics supplementation and syphilis testing. Some post-strike ‘’catch-up” activity occurred, however this may have been too late in some instances.ConclusionsPolicy-makers at national and county level need to ensure population health is protected at times of strikes and ideally resolve disputes without such action. Not to do so risks major negative effects on maternal and child health. Increased use of the non-public health sector could be done by the authorities in mitigation should strikes occur again.

Influence of test parameters on the interlaminar shear strength of FRP bars

At present, the interlaminar shear test is increasingly used as a supplementary test to determine the mechanical characteristics of FRP bars. This is mainly due to its simplicity and its ability to quantify the properties of the fibre/matrix interface. These tests are performed according to ASTM D4475. However, there are several parameters in ASTM D4475 that are not directly specified. Due to this, studies that use such tests feature a variety of different boundary conditions and, consequently, suffer from limited comparability. Furthermore, no study is available in which the effects of changes in selected parameters are comprehensively determined. This paper presents an experimental study that investigated the capabilities and limitations of the short-beam test. In this study a total of 338 specimens from three different manufacturers were tested. The study was focused on the influence of different bar diameters, span-to-diameter ratios and loading speeds. It was found experimentally that the calculated interlaminar shear strength is strongly affected by the applied span-to-diameter ratio. Therefore, the article offers a conversion relationship that takes the span-to-diameter ratio into account. The suitability of the conversion relationship was also verified for alkali-conditioned specimens.

The user experience design of a novel microscope within SurgiSim, a virtual reality surgical simulator.

PurposeVirtual reality (VR) simulation has the potential to advance surgical education, procedural planning, and intraoperative guidance. “SurgiSim” is a VR platform developed for the rehearsal of complex procedures using patient-specific anatomy, high-fidelity stereoscopic graphics, and haptic feedback. SurgiSim is the first VR simulator to include a virtual operating room microscope. We describe the process of designing and refining the VR microscope user experience (UX) and user interaction (UI) to optimize surgical rehearsal and education.MethodsHuman-centered VR design principles were applied in the design of the SurgiSim microscope to optimize the user’s sense of presence. Throughout the UX’s development, the team of developers met regularly with surgeons to gather end-user feedback. Supplemental testing was performed on four participants.ResultsThrough observation and participant feedback, we made iterative design upgrades to the SurgiSim platform. We identified the following key characteristics of the VR microscope UI: overall appearance, hand controller interface, and microscope movement.ConclusionOur design process identified challenges arising from the disparity between VR and physical environments that pertain to microscope education and deployment. These roadblocks were addressed using creative solutions. Future studies will investigate the efficacy of VR surgical microscope training on real-world microscope skills as assessed by validated performance metrics.

Characterization of Reference Materials for TPMT and NUDT15: A GeT-RM Collaborative Project

Pharmacogenetic testing is increasingly provided by clinical and research laboratories; however, only a limited number of quality control and reference materials are currently available for many of the TPMT and NUDT15 variants included in clinical tests. To address this need, the Division of Laboratory Systems, Centers for Disease Control and Prevention-based Genetic Testing Reference Material (GeT-RM) coordination program, in collaboration with members of the pharmacogenetic testing and research communities and the Coriell Institute for Medical Research, has characterized 19 DNA samples derived from Coriell cell lines. DNA samples were distributed to four volunteer testing laboratories for genotyping using a variety of commercially available and laboratory developed tests and/or Sanger sequencing. Of the 12 samples characterized for TPMT, newly identified variants include TPMT∗2, ∗6, ∗12, ∗16, ∗21, ∗24, ∗32, ∗33, and ∗40; for the 7 NUDT15 reference material samples, newly identified variants are NUDT15∗2, ∗3, ∗4, ∗5, ∗6, and ∗9. In addition, a novel haplotype, TPMT∗46, was identified in this study. Preexisting data on an additional 11 Coriell samples, as well as some supplemental testing, were used to create comprehensive reference material panels for TPMT and NUDT15. These publicly available and well-characterized materials can be used to support the quality assurance and quality control programs of clinical laboratories performing clinical pharmacogenetic testing.

A Paired Comparison of Plasma and Bronchoalveolar Lavage Fluid for Metagenomic Next-Generation Sequencing in Critically Ill Patients with Suspected Severe Pneumonia.

PurposePlasma metagenomic next-generation sequencing (mNGS) has emerged as an attractive and minimally invasive technique for pathogen detection. However, few studies have demonstrated the need for simultaneous plasma and bronchoalveolar lavage fluid (BALF) mNGS in patients with severe pneumonia.Patients and MethodsThis study retrospectively performed a paired comparison of BALF and plasma mNGS in critically ill patients with suspected severe pneumonia from April 2019 to December 2020. The diagnostic performance of BALF and plasma mNGS was compared using the clinical composite diagnosis as the reference standard.ResultsIn total, 57 patients were included in this study. Patients with positive plasma mNGS had shorter hospital stay days at the time of specimen acquisition (4.5 vs 11, P = 0.028) and a higher positivity rate of BALF culture (50% vs 22.9%, P = 0.033) than patients with negative plasma mNGS. Fifty-three patients (93%) were finally diagnosed with severe pneumonia. Significant differences were observed in the sensitivity of BALF and plasma mNGS (100% vs 42%, P < 0.001), and the diagnostic accuracy was 96% and 46%, respectively. The proportion of virus in positive plasma mNGS results was higher than that in BALF mNGS (23% vs 11%, P = 0.173) without significant difference. Although plasma mNGS detected additional microorganisms in 11/53 patients, the beneficial effect was observed in only 5/53 (9%) patients.ConclusionIn this study, the clinical effect of simultaneously conducting mNGS of BALF and plasma samples was found to be limited. For patients with the suspected virus infection, plasma mNGS may be a supplementary test. Further studies are needed to identify the optimal indications for plasma mNGS.

Phototransferred thermoluminescence of CaF2: Principles, analytical methods, and mechanisms

Phototransferred thermoluminescence (PTTL) of natural fluorite induced by 470 nm blue-, 525 nm green-, and 870 nm infrared light is reported. Although its conventional thermoluminescence (TL) glow curve measured during heating to 600 °C has six peaks, only five are reproduced under phototransfer. One of them corresponds to a hole trap. The sixth peak counterintuitively increases in intensity with illumination in a change suggestive of competition effects involving deep electron traps. The dependence of PTTL intensity on duration of illumination for each PTTL peak is analyzed using phenomenological and kinetic models as systems of acceptors and donors with the number of the latter informed by experiment. The intensity of PTTL increases with the temperature of illumination with an activation energy of thermal assistance of 0.14 ± 0.01 eV and decreases at elevated temperatures with an activation energy of thermal quenching of 1.1 ± 0.3 eV. The long-term behavior of time-response profiles and the interaction of holes with stimulated electrons as studied by stability theory show unstable critical points. Supplementary tests show that exposing CaF2 to UV illumination achieves the same effect as beta irradiation, and any resultant peaks relate to conventional TL rather than phototransfer.

Performance of HIV rapid testing algorithm in Nigeria: Findings from a household-based Nigeria HIV/AIDS Indicator and Impact Survey (NAIIS).

The Nigeria AIDS Indicator and Impact Survey (NAIIS), a cross-sectional household survey, was conducted in 2018 with primary objectives to estimate HIV prevalence, HIV-1 incidence, and status of UNAIDS 90-90-90 cascade. We conducted retrospective analysis of the performance of HIV rapid tests and the national HIV testing algorithm used in Nigeria. The national algorithm included Determine HIV-1/2 as test 1 (T1), Unigold HIV-1/2 as test 2 (T2), and StatPak HIV-1/2 as the tie-breaker test (T3). Individuals reactive with T1 and either T2 or T3 were considered HIV-positive. HIV-positive specimens from the algorithm were further confirmed for the survey using supplemental test Geenius HIV-1/2. If Geenius did not confirm HIV-positive status, HIV-1 Western blot was performed. We calculated the concordance between tests and positive predictive value (PPV) of the algorithm on unweighted data. Of 204,930 participants (ages ≥18 months) 5,103 (2.5%) were reactive on T1. Serial testing of T1 reactive specimens with T2 or if needed by tiebreaker T3 identified 2958 (1.44%) persons as HIV-positive. Supplemental testing confirmed 2,800 (95%) as HIV-positive (HIV-1 = 2,767 [98.8%]; HIV-2 = 5 [0.2%]; dual infections = 22 [0.8%]). Concordance between T1 and T2 was 56.6% while PPV of the national algorithm was 94.5%. Our results show high discordant rates and poor PPV of the national algorithm with a false-positive rate of about 5.5% in the NAIIS survey. Considering our findings have major implications for HIV diagnosis in routine HIV testing services, additional evaluation of testing algorithm is warranted in Nigeria.

Investigating the effectiveness of supplemental breast cancer screening tests considering radiologists’ bias

Breast density is known to increase breast cancer risk and decrease mammography screening sensitivity. Breast density notification laws require physicians to inform women with high breast density of these potential risks. The laws usually require healthcare providers to notify patients of the possibility of using more sensitive supplemental screening tests (i.e., ultrasound and MRI). Since the enactment of the laws, there have been controversial debates over (i) their implementations due to the potential radiologists’ bias in breast density classification of mammogram images and (ii) the necessity of supplemental screenings for all patients with high breast density. In this study, we formulate a finite-horizon, discrete-time partially observable Markov chain to investigate the effectiveness of supplemental screening and the impact of radiologists’ misclassification bias on patients’ outcomes. We consider the conditional probability of eventually detecting breast cancer in early states given that the patient develops breast cancer in her lifetime as the primary and the expected number of supplemental tests as the secondary patient’s outcome. Our results indicate that referring patients to a supplemental test solely based on their breast density may not necessarily improve their health outcomes and other risk factors need to be considered when making such referrals. Additionally, average-skilled radiologists’ performances are shown to be comparable with the performance of a perfect radiologist (i.e., 100% accuracy in breast density classification). However, a significant bias in breast density classification (i.e., consistent upgrading or downgrading of breast density classes) can negatively impact a patient’s health outcomes.

Bilateral yellow plaques on the upper eyelids

Bilateral yellow plaques on the upper eyelids

Does combining different types of innovation always improve SME performance? An analysis of innovation complementarity

Small- and medium-sized enterprises (SMEs) sometimes introduce different types of innovation simultaneously. However, the performance implications of simultaneous innovation practices remain under-researched in the literature. Therefore, this paper explores the combined use of six types of innovation and examines complementarity/substitutability in performance between these types of innovation. Data for the empirical analysis originates from a sample of 1,139 Chinese manufacturing SMEs. We identify two tendencies of simultaneous innovation by means of exploratory factor analysis (EFA), which are as follows: product-oriented and production-oriented. Using a conditional approach to supermodularity, we find no interplay between product-oriented types of innovation, but substitutability between production-oriented types of innovation. Based on organizational literature, we perform a supplementary test for the relationship between production-oriented types of innovation and organizational innovation. The result shows that substitutability between production-oriented types of innovation exists only in the absence of organizational innovation. These findings suggest that SMEs in China derive only additive benefits from a combination of product-oriented innovation, and gain no performance payoff from a combination of production-oriented innovation unless they introduce simultaneous organizational change.

Breast Cancer Screening and Diagnostic Advancements

The best tool to detect breast cancer (BC) is `screening`. Earlier screening improves prognosis and better treatment outcomes. Screening is basically looking for different signs before the appearance of actual symptoms. The process of screening specifically used for BC is known as mammography.&#x0D; Mammography is an explicit kind of imaging system that uses X-Rays (low dose) to ascertain cancer in breasts. This diagnostic procedure is in practice since the past 30 years but in the past 15 years, there is an improved set of techniques being introduced resulting in better results. Recently, three major diagnostic procedures for breast cancer which are in vogue include digital mammography, computer-aided testing and tomosynthesis. Out of these 3 diagnostic tools, tomosynthesis, furthermore branded as three-dimensional (3-D) mammography and digital tomosynthesis, is the supreme and innovative system of breast imaging where numerous pictures of the breast from diverse angles are taken and remodeled ("synthesized") resulting in formation of a three-dimensional group of images. That is why, 3-D imaging technique is alike computed tomography imaging system in which a sequences of thin "slices" are gathered to formulate a 3-D reformation of the body.&#x0D; Even though the strength of radiation for few tomosynthesis systems is higher to some extent as compared to power of the dosage used in typical mammography, but as long as it is in the predefined radiation limit approved by FDA it`s not harmful. Some of the systems have doses comparable to conventional mammography. Some previous studies on large populations have proved that breast screening with tomosynthesis have resulted in enhanced the rate of detection of breast cancer detection rates and it has also decreased the chances of recalls, especially at occasions where females are called back for screening for added testing because of a possibly uncharacteristic finding.&#x0D; Tomosynthesis has an edge on other diagnostic procedures as it may help in prior recognition of cancerous lesions that may be not be revealed on a conventional mammogram, it also eradicates the need for small number of preventable biopsies or supplementary testing and increases the probability of detection of several breast tumors. It also provides stronger imagining of irregularities within condensed breast tissue and greater precision in pinpointing the location, size and shape of breast anomalies.&#x0D; Women should at least get a standard mammogram once a year beginning at age 40. The major risk factors for BC development are old age, inactivity, reproductive history, genetic mutations, family history of ovarian or BC, being overweight or obese after menopause, history of administration of hormones. Also, if someone, have had radiation treatment to the chest in the past, it’s highly recommended that such women should have annual mammograms at a younger age (often beginning around age 30).

Striving to improve investment efficiency among Chinese firms: does the role of venture capital matter?

PurposeThis study aims to investigate the impact of venture capital (VC) involvement on investment efficiency (IE) and its potential action mechanisms from the perspective of financial resource allocation.Design/methodology/approachUsing data of Chinese firms between 2008 and 2020, and the propensity score matching–difference in differences method, the authors investigate the relationship between VC and IE.FindingsThe results show that VC involvement significantly promotes IE, and the effect exhibits an inverted U-shape dynamic over time. The authors find two mechanisms through which VC promotes IE: alleviating financing constraints and improving corporate governance. Supplementary tests indicate that VC institutions with high reputations play a significant role in enhancing IE; the promotion effect is more pronounced for firms in non-high-tech industries, firms facing higher industrial competition and firms located in areas with better property rights protection systems.Originality/valueThis study provides several original contributions. First, based on principal–agent and financing constraint theories, this study enhances the literature by revealing how VC drives the IE of newly public firms in China. Second, to the best of the authors’ knowledge, this is the first attempt to identify the mechanisms between VC and IE; Third, from an empirical perspective, besides discussing the average and dynamic effect of VC on IE, this study also explores the impact of the interaction between VC and market competition and property rights protection on IE.

IgM Positivity for Both EBV and CMV: A Clinical Conundrum.

A review of 28 patients who tested positive for both Epstein-Barr virus and cytomegalovirus immunoglobulin M at an academic medical center revealed that dual positivity is more common than previously reported. These cases require careful review of the history and sometimes supplemental testing. This report highlights features of patients with dual positivity and provides recommendations on interpretation of the results.

A New Trial to Measure ABO Antibodies Using Complement-Dependent Cytotoxicity.

Background and objectives: The ABO antibody (Ab) titration tests are used in monitoring in ABO-incompatible (ABOi) solid organ transplantation (SOT). However, currently developed ABO Ab tests show Ab binding reactions. This study attempted to measure ABO Ab level using complement-dependent cytotoxicity (CDC). Materials and methods: We studied 93 blood group O serum samples from patients who underwent ABOi SOT from January 2019 to May 2021. Patients’ sera were incubated with A1 or B cells and added to a human complement solution. Supernatants were collected after centrifugation, and free hemoglobin (Hb) was measured by spectrophotometry. We converted plasma Hb value to hemolysis (%), which were compared with ABO Ab titer. Results: We found a mild correlation between hemolysis and ABO Ab titers. In simple regression analysis, the correlation coefficients were within 0.3660–0.4968 (p < 0.0001) before transplantation. In multiple linear regression analysis, anti-A hemolysis (%) was higher in immunoglobulin M (IgM) (β = 12.9) than in immunoglobulin G (IgG) (β = −3.4) (R2 = 0.5216). Anti-B hemolysis was higher in IgM (β = 8.7) than in IgG (β = 0.0) (R2 = 0.5114). There was a large variation in hemolysis within the same Ab titer. Conclusions: CDC can be used in a new trial for ABO Ab measurement. Furthermore, IgM rather than IgG seems to play a significant role in vivo activity, consistent with previous knowledge. Thus, this study may help in the development of the ABO Ab titration supplement test for post-transplant treatment policy establishment and pre-transplant desensitization.

Abstract 3069: Efficient establishment and utilization of a high-grade serous ovarian cancer organoid biobank

Abstract Extensive utilization of organoids from high-grade serous ovarian carcinoma (HGSOC), the most common and lethal ovarian cancer, has been hampered by low success rates of long-term culture and scarcity of fresh tumor material. Here we present the development of a novel method for efficient generation, expansion and use of HGSOC organoids from cryopreserved tumor material. First, we assessed commonly used organoid media components and found that supplements such as FGF-2, R-Spondin1, Wnt or Noggin had negative impact on the HGSOC organoid derivation. But further, we found that supplementation with FGF-4, which has not been used in cancer organoid culture before, is beneficial for HGSOC organoid growth. Through extensive testing of various supplements and their combinations, we designed two novel HGSOC organoid media formulations - Medium 1 (M1) and Medium 2 (M2). Using M1 and M2 enabled generation and long-term expansion of living HGSOC organoid biobank with markedly improved success rate than in previous reports (55% vs. 23-38%). The organoids were established from cryopreserved tumor material, demonstrating the feasibility of using frozen tissue biobanks for HGSOC organoid derivation. Overall, we generated a collection of 18 expandable HGSOC organoid lines from 11 patients, encompassing samples from different tissue sites and disease progression stages. We validated the organoids using whole-genome sequencing, immunohistochemistry and single-cell RNA sequencing and demonstrated that they are genetically and phenotypically representative of original patient samples over long-term culture. Based on available patient consents, we deposited 3 organoid lines in a publicly accessible biobank. Finally, we investigated whether organoid drug responses correlate to those observed earlier in the clinic in the corresponding patients. Organoid-based drug-response profiling of clinically used HGSOC drug collection was performed in 384-well microplate format. To explore whether growth conditions impact correlation between organoid drug responses and clinical response, we compared the organoid drug responses in the nutrient-rich M1/M2 growth media to the ones observed in human plasma-like medium (HPLM), supplemented with relevant niche factors from M1/M2. Organoid drug responses correlated with clinical treatment outcomes, but only for organoids maintained in HPLM (Spearman r = 0.987, p=0.007 in HPLM vs 0.607, p=0.167 in growth medium, n=7), highlighting the importance of culture conditions in organoid-based functional assays. Taken together, we introduce a resource for efficient development and use of HGSOC organoids from cryopreserved material in ovarian cancer research. Citation Format: Wojciech Senkowski, Laura Gall Mas, Matias M. Falco, Yilin Li, Kari Lavikka, Mette C. Kriegbaum, Jaana Oikkonen, Daria Bulanova, Elin J. Pietras, Karolin Voßgröne, Erdogan P. Erkan, Terese K. Høj, Mia K. Høg, Tarja Lamminen, Katja Kaipio, Anni Virtanen, Lars H. Engelholm, Pernille Christiansen, Eric Santoni-Rugiu, Kaisa Huhtinen, Olli Carpén, Johanna Hynninen, Sampsa Hautaniemi, Anna Vähärautio, Krister Wennerberg. Efficient establishment and utilization of a high-grade serous ovarian cancer organoid biobank [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3069.

Perceived cost of newly prescribed medication and supplementary diagnostic tests in the elderly: An experimental approach

Primary nonadherence to medical prescription is a notorious phenomenon among the elderly. The perceived cost of medication and supplementary diagnostic tests is a major factor driving prescription adherence decisions. To explore the way such factor impinges on the perception of prescription cost, two independent samples of elderly volunteers (medication, N=59; supplementary diagnostic tests, N=58) rated on a visual analogue scale specific amounts of money matching three proportions of income reduction of a fictitious patient. Both medication and supplementary diagnostic tests modalities of prescription showed participants’ perception of cost to notoriously vary in the 3% and the 30% proportions of prescription values to the fictitious patient’s income, but not in the 15%. Further, Different patterns of perceived cost response suggest that an element of intertemporal choice influenced cost perception. Participants’ income had had no impact on their perception of cost, contrary to the pattern of self-referent responses that “perspective-taking” approaches would suggest. Further, research would benefit from broadening these experimental settings to include other known factors impacting nonadherence along with cost.

ANALYSIS OF THE INFLUENCE OF CORPORATE SOCIAL RESPONSIBILITY (CSR), COMPANY SIZE AND LEVERAGE ON FIRM VALUE WITH PROFITABILITY MEDIATION VARIABLES ON MINING COMPANY LISTED ON THE IDX (BEFORE COVID-19 2016-2019 AND DURING COVID-19 2020)

The purpose of this study was to analyze the effect of Corporate Social Responsibility (CSR), company size, and leverage on firm value by using the moderating variable of profitability in mining companies listed on the IDX (2016-2020). The number of samples in the companies studied was 27 companies. The research used a purposive sampling method to determine the selection. Data analysis using multiple regression analysis and also an endurance test The results of this study are Corporate Social Responsibility (CSR) has no effect on firm value. Company size has no effect on firm value. Leverage has no significant effect on firm value. All moderating relation also variable cannot be proven. Hence this research then made supplementary test by divided the timeline after and during covid. The results shows that the insignificant of data due to different situation before covid and during covid. Before covid period (2016-2019) the results consistent with main hypothesis testing. Thus, during Covid-19 profitability moderate the relations between company size and firm value during 2020. The implication of this research is to help investors make investment decisions and help companies optimize the company.

Clinical Application Evaluation of Elecsys® HIV Duo Assay in Southwest China.

BackgroundHIV/AIDS continues to be a serious health concern of morbidity and mortality globally, and novel HIV testing is still an important component of diagnosing HIV earlier and reducing the spread of HIV. The Elecsys® HIV Duo assay is a 4th generation assay that can detect both HIV-1 p24 antigen (Ag) and HIV-1/2 antibody (Ab) in parallel and show the subresults for the Ab and Ab units.ObjectivesTo evaluate the clinical performance of the Elecsys® HIV Duo assay on the new cobas E 801 analyzer using a large number of clinical samples from a population in southwest China.MethodsWe collected testing results and information from all patients in a large general hospital. All eligible clinical specimens were first analyzed using the Elecsys® HIV Duo assay. The test results are given either as reactive or nonreactive as well as in the form of a cutoff index (COI). All initially reactive specimens were retested in duplicate with a 3rd-generation kit. Supplementary tests were divided into Ab confirmation tests and HIV-1 nucleic acid tests. GraphPad Prism and Python were used for plotting, and SPSS 21.0 software was used for statistical analysis.ResultsA total of 186391 specimens were received, and 436 patients were confirmed to be positive for HIV. Among the 86 cases with contact history available, there were more males than females, and heterosexual transmission was the most common route of HIV infection. The Elecsys® HIV Duo assay displayed 99.94%, 99.93% and 99.98% specificity for inpatient, outpatient and physical examination patients, respectively. The median COI ratios of the false-positive group were significantly lower than those of the true-positive group.ConclusionsThe Elecsys® HIV Duo test (Cobase801 analyzer) differentiates the detection of HIV-1 p24 Ag and HIV-1/2 Ab with high specificity and facilitates the diagnosis of patients with early HIV infection. Therefore, the Elecsys®HIV Duo test is used for differentiation of antigen and antibody reactivity, making it suitable for routine clinical diagnosis.

Knee-Spine Syndrome: Management Dilemma When Knee Osteoarthritis Coexists With Spine Degeneration.

The elderly present with progressive degenerative osteoarthritis of the knee and lumbar spine degeneration (LSD). The coexistent conditions when presented concurrently become challenging for the clinicians and surgeons, as well as determining the predominant source of the underlying pain generation factor. The concurrent presentation of a significant knee and low back pain poses challenges in decision-making for treatment with management being normally individualized.The review narrates the different concepts used for the assessment of knee-spine syndrome. The prime factor for the pain needs to be ascertained by evaluating the deformity of the lumbar spine and the knees to address the causative factor appropriately. A thorough history, detailed examination, and supplemental diagnostic testing will differentiate the clinical entities and guide the treatment. However, a misdiagnosis may need a secondary site surgery and further treatment to alleviate the pain. Clinicians have been challenged while differentiating between the knee and spine pathology to target prime pain generator factors for adequate pain relief, improved functional outcomes, and substantial patient satisfaction. We present our strategy for the management of knee-spine syndrome. The protocols utilized to manage the clinical scenario have been reviewed and discussed. Clinical pearls to identify and treat the symptomatic concurrent knee-spine degeneration are presented.There is still a lack of consensus on the concurrent knee-spine degenerative pathology and its management strategy. The dilemma persists, and a case-based approach needs to be adopted by surgeons.

17α‐Estradiol Mitigates the Negative Effects of High‐Fat Feeding in Both Male and Female Mice

17α‐estradiol (17α‐E2) is an endogenous, non‐feminizing enantiomer of 17β‐estradiol. 17α‐E2 supplementation improves the lifespan of male, but not female, mice through metabolic mechanisms. Although the effects of 17α‐E2 on liver and adipose tissue are well described, potential benefits in skeletal muscle are unknown. The objective of this study was to determine if 17α‐E2 can mitigate the negative effects of a high‐fat diet (HFD) on skeletal muscle metabolism. In addition, we sought to determine if there were sex differences in these responses. We hypothesized that 17α‐E2 supplementation would ameliorate the negative effects of a HFD in skeletal muscle of male, but not female mice. To test this hypothesis, wild type male (n=19) and female (n=15) mice began a HFD (45% fat) at 3 months of age. At 9 months of age, half of the males (n=10) and females (n=8) received diets supplemented with 17α‐E2 (14.4ppm) for 3.5 months. Mice underwent weekly assessment of body composition by QMR throughout the 17α‐E2 supplementation, while glucose and insulin tolerance tests were completed 8 weeks into treatment. Leg muscles were harvested and analyzed for inflammatory cytokines via RT‐qPCR, fat infiltration via Oil Red O (ORO) staining, and triglyceride content. 17α‐E2 reduced whole‐body fat mass (p = 0.001, 11.6% ± 0.4%) and whole‐body lean mass (p = 0.003, 3.5% ± 0.2) in males. In females, 17α‐E2 reduced fat mass (p = 0.0001, 33.1% ± 1.1%), but did not alter lean mass (p = 0.99, 0.9% ± 0.2%). There were no changes in the mass of the quadriceps, gastrocnemius, soleus, tibialis anterior or extensor digitorum longus muscles in males or females (p &gt; 0.05). 17α‐E2 improved glucose tolerance in females (p = 0.03, 22301 ± 573 AUC and 33022 ± 1663 AUC) but not in males (p = 0.11, 24856 ± 159 AUC and 29968 ± 466 AUC). 17α‐E2 reduced insulin resistance in males (p = 0.001, 14784 ± 326 AUC and 19220 ± 246 AUC) and females (p = 0.05, 10992 ± 315 AUC and 14644 ± 540 AUC). 17α‐E2 reduced the expression of IL‐6 (p = 0.005), IL‐1α (p = 0.002), and TNFα (p &lt; 0.001) in males, but 17α‐E2 did not change cytokine expression in females (p &gt; 0.05). There was no difference in gastrocnemius ORO staining in the males (p = 0.59) or females (p = 0.68). 17α‐E2 supplementation did not change quadricep triglycerides in males (p = 0.98, 25.6 ± 1.6 mg/g and 27.3 ± 1.7 mg/g). However, females on 17α‐E2 had significantly lower quadricep triglycerides compared to HFD (p = 0.03, 13.6 ± 1.1 mg/g and 26.6 ± 0.7 mg/g). These results suggest that long term 17α‐E2 supplementation ameliorates the effects of a HFD on skeletal muscle in both males and females but in a sex dimorphic manner. Further research is needed to determine how 17α‐E2 supplementation alters skeletal muscle metabolism in both sexes.