Root-to-shoot signaling positively mediates source-sink relation in late growth stages in diploid and tetraploid wheat.

Non-hydraulic root source signaling (nHRS) is a unique positive response to soil drying in the regulation of plant growth and development. However, it is unclear how the nHRS mediates the tradeoff between source and sink at the late growth stages and its adaptive mechanisms in primitive wheat. To address this issue, a root-splitting design was made by inserting solid partition in the middle of the pot culture to induce the occurrence of nHRS using four wheat cultivars (MO1 and MO4, diploid; DM22 and DM31, tetraploid) as materials. Three water treatments were designed as 1) both halves watered (CK), 2) holistic root system watered then droughted (FS), 3) one-half of the root system watered and half droughted (PS). FS and PS were designed to compare the role of the full root system and split root system to induce nHRS. Leaves samples were collected during booting and anthesis to compare the role of nHRS at both growth stages. The data indicated that under PS treatment, ABA concentration was significantly higher than FS and CK, demonstrating the induction of nHRS in split root design and nHRS decreased cytokinin (ZR) levels, particularly in the PS treatment. Soluble sugar and proline accumulation were higher in the anthesis stage as compared to the booting stage. POD activity was higher at anthesis, while CAT was higher at the booting stage. Increased ABA (nHRS) correlated with source-sink relationships and metabolic rate (i.e., leaf) connecting other stress signals. Biomass density showed superior resource acquisition and utilization capabilities in both FS and PS treatment as compared to CK in all plants. Our findings indicate that nHRS-induced alterations in phytohormones and their effect on source-sink relations were allied with the growth stages in primitive wheat.

Alternative Approaches for the Management of Urinary Tract Infection with Crano-cure: A Randomized Clinical Trial.

Background: Urinary tract infection (UTI) is a renal infection that affects the urinary tract and is global problem related to health and many people are affected each year at some points of their lives. Modern studies about urinary tract infections show that almost one third of the world's population has been suffering from this ailment. Different antibacterial medicines have been reported to have resistance against pathogens. In order to overcome the problem, exploration for new and dynamic antibacterial agents from natural sources is the emerging trend. Primary Study Objective: The primary objective was to evaluate the efficacy and safety of the polyherbal test drug formulation, "Crano-cure", as treatment for UTIs. Methods/Design: In the current study, clinical trials were designed to evaluate the effects of the polyherbal formulation "Crano-cure" compared to the standard drug Ciprofloxacin in randomized, controlled multicenter trial of 205 patients, analyzing clinical outcomes and safety profiles. Setting and Participants: Conducted across multiple centers, including Shifa-ul-Mulk Memorial Hospital at Hamdard University Karachi and three other clinics, the study involved 205 patients aged 15-60, irrespective of their socioeconomic status. Intervention: Patients were classified into two groups i.e. control group (ciprofloxacin) and the test group (crane-cure). Polyherbal formulation of 500 mg Crano-cure capsules two times in a day were administered to the test group for 28 days. The control group was administered a control ciprofloxacin tablet 500 mg two times in a day for 28 days. Primary Outcome Measures: The drug was found safe for further clinical study after observing changes or improvements in UTI symptoms, urine culture and blood complete tests. The clinical trial was dully registered on the US National Library of Medicine, ClinicalTrials.gov Identifier: NCT04575493. The trial was accompanied in the instructions of EC (Ethical Committee). The study plan and procedures were displayed to the BASR (Board of Advance Studies and Research) and board members of the Ethical Committee (EC), which was ERB-2021-9-1. Results: Clinical study results revealed the effectiveness of Crano-cure in the management of UTIs symptoms and hematological and biochemical parameters including blood complete test, liver function tests, renal function tests and lipid profile. Moreover, the test drug Crano-cure revealed a significance level (P ≤ .05) in compliance and cost-effectiveness compared to control ciprofloxacin. Conclusion: In conclusion, Crano-cure is a safe and cost-effective alternate to Ciprofloxacin for treatment of UTIs.

Protein kinase CK2 - diverse roles in cancer cell biology and therapeutic promise.

The association of protein kinase CK2 (formerly casein kinase II or 2) with cell growth and proliferation in cells was apparent at early stages of its investigation. A cancer-specific role for CK2 remained unclear until it was determined that CK2 was also a potent suppressor of cell death (apoptosis); the latter characteristic differentiated its function in normal versus malignant cells because dysregulation of both cell growth and cell death is a universal feature of cancer cells. Over time, it became evident that CK2 exerts its influence on a diverse range of cell functions in normal as well as in transformed cells. As such, CK2 and its substrates are localized in various compartments of the cell. The dysregulation of CK2 is documented in a wide range of malignancies; notably, by increased CK2 protein and activity levels with relatively moderate change in its RNA abundance. High levels of CK2 are associated with poor prognosis in multiple cancer types, and CK2 is a target for active research and testing for cancer therapy. Aspects of CK2 cellular roles and targeting in cancer are discussed in the present review, with focus on nuclear and mitochondrial functions and prostate, breast and head and neck malignancies.

The Efficacy of Kundur (Boswellia serrata Roxb. Ex Colebr.) in Vulvovaginal Candidiasis: A Randomized Control Trial.

Context: Kundur, Boswellia serrata Roxb. ex Colebr., is prescribed by Unani (Greco-Arab) scholars clinically under conditions similar to vulvovaginal candidiasis (VVC) and has been supported by recent pharmacological studies, but scientific evidence is scarce. Objectives: The study intended to investigate the drug's scientific parameters and to compare its efficacy and safety to that of Miconazole nitrate (2% w/w) in treatment of VVC. Design: The research team designed a randomized controlled trial (RCT). Setting: The RCT was performed in the Department of Ilmul Qabalat wa Amraze Niswan at Luqman Unani Medical College Hospital and Research Center in Vijaypura, India, between November 2018 and March 2020. Participants: Participants were 40 married women, aged 18 to 45 years, who had been clinically examined and diagnosed with VVC. Interventions: Participants were randomly allocated to the Boswellia serrata (Kundur) group, the intervention group (n = 20), or to the miconazole group, the control group (n = 20). The Kundur group took a one-gram tablet of Kundur as a vaginal insert every day at bedtime for 21 days, while the control group used vaginal suppositories with 100 mg of miconazole (2% w/w) every day at bedtime for seven days. Outcome Measures: The primary outcome measures were changes: (1) in vulval itching (pruritus), (2) in vaginal discharge, (3) in painful urination (dysuria), (4) in recurrent genital pain (dyspareunia), and (5) in quality of life (QoL). The secondary outcome measures were mycological clearing on a potassium hydroxide (KOH) test and a per-speculum pelvic examination for the presence or absence of curdy discharge, vulval erythema, and vulval swelling. Results: The response to the intervention was greater than that of the control in reducing pruritus vulvae and vaginal discharge. However, both drugs were equally effective in improving the rest of the parameters, including QoL. Conclusion: The VVC symptoms were equally and significantly improved in both the intervention and the control groups, and Boswellia serrata Roxb. ex Colebr. was shown to be efficacious in the management of VVC. Further studies with a rigorous design and larger sample size are needed to reinforce scientific evidence.

Evaluation the Effectiveness of Abridged IMNCI (7-Day) Course v Standard (11-Day) Course in Pakistan.

BACKGROUND: The conventional IMCI training for healthcare providers is delivered in 11 days, which can be expensive and disruptive to the normal clinical routines of the providers. An equally effective, shorter training course may address these challenges. METHODS: We conducted a quasi-experimental study in two provinces (Sindh and Punjab) of Pakistan. 104 healthcare providers were conveniently selected to receive either the abridged (7-day) or the standard (11-day) training. Knowledge and clinical skills of the participants were assessed before, immediately on conclusion of, and six months after the training. RESULTS: The improvement in mean knowledge scores of the 7-day and 11-day training groups was 31.6 (95% CI 24.3, 38.8) and 29.4 (95% CI 23.9, 34.9) respectively, p = 0.630 while the improvement in mean clinical skills scores of the 7-day and 11-day training groups was 23.8 (95% CI: 19.3, 28.2) and 23.0 (95% CI 18.9, 27.0) respectively, p = 0.784. The decline in mean knowledge scores six months after the training was - 12.4 (95% CI - 18.5, - 6.4) and - 6.4 (95% CI - 10.5, - 2.3) in the 7-day and 11-day groups respectively, p = 0.094. The decline in mean clinical skills scores six months after the training was - 6.3 (95% CI - 11.3, - 1.3) in the 7-day training group and - 9.1 (95% CI - 11.5, - 6.6) in the 11-day group, p = 0.308. CONCLUSION: An abridged IMNCI training is equally effective as the standard training. However, training for certain illnesses may be better delivered by the standard course.

Single-bone versus both-bone plating of unstable paediatric both-bone forearm fractures. A randomized controlled clinical trial.

PURPOSE: This clinical trial compares the functional and radiological outcomes of single-bone fixation to both-bone fixation of unstable paediatric both-bone forearm fractures. METHODS: This individually randomized two-group parallel clinical trial was performed following the Consolidated Standards of Reporting Trials (CONSORT) statement at a single academic tertiary medical centre with an established paediatric orthopaedics unit. All children aged between nine and 15 years who presented to the emergency department at Assiut university with unstable diaphyseal, both-bone forearm fractures requiring surgical intervention between November 1, 2018, and February 28, 2020, were screened for eligibility against the inclusion and exclusion criteria. Inclusion criteria were diaphyseal unstable fractures defined as shaft fractures between the distal and proximal metaphyses with an angulation of > 10°, and/or malrotation of > 30°, and/or displacement > 10 mm after attempted closed reduction. Exclusion criteria included open fractures, Galeazzi fractures, Monteggia fractures, radial head fractures, and associated neurovascular injuries. Patients who met the inclusion criteria were randomized to either the single-bone fixation group (intervention) or the both-bone fixation group (control). Primary outcomes were forearm range of motion and fracture union, while secondary outcomes were forearm function (price criteria), radius re-angulation, wrist and elbow range of motion, and surgical time RESULTS: A total of 50 children were included. Out of these 50 children, 25 were randomized to either arm of the study. All children in either group received the treatment assigned by randomization. Fifty (100%) children were available for final follow-up at six months post-operatively. The mean age of single-bone and both-bone fixation groups was 11.48 ± 1.93 and 13 ± 1.75 years, respectively, with a statistically significant difference (p = 0.006). There were no statistically significant differences in gender, laterality, affection of the dominant hand, or mode of trauma between single-bone and both-bone fixation groups. All patients in both groups achieved fracture union. There mean radius re-angulation of the single-bone fixation groups was 5.36 ± 4.39 (0-20) degrees, while there was no radius re-angulation in the both-bone fixation group, with a statistically significant difference (p < 0.001). The time to union in the single-bone group was 6.28 ± 1.51 weeks, while the time to union in the both-bone fixation group was 6.64 ± 1.75 weeks, with no statistically significant difference (p = 0.44). There were no infections or refractures in either group. In the single-bone fixation group, 24 (96%) patients have regained their full forearm ROM (loss of ROM < 15°), while only one (4%) patient lost between 15 and 30° of ROM. In the both-bone fixation group, 23 (92%) patients have regained their full forearm ROM (loss of ROM < 15°), while only two (8%) patients lost between 15 and 30° of ROM. There was no statistically significant difference between groups in loss of forearm ROM (p = 0.55). All patients in both groups regained full ROM of their elbow and wrist joints. On price grading, 24 (96%) and 23 (92%) patients who underwent single bone fixation and both-bone fixation scored excellent, respectively. Only one (4%) patient in the single-bone fixation group and two (8%) patients in the both-bone fixation group scored good, with no statistically significant difference in price score between groups (p = 0.49). The majority of the patients from both groups had no pain on the numerical pain scale; 22 (88%) patients in the single-bone fixation group and 21 (84%) patients in the both-bone fixation groups, with no statistically significant difference between groups (p = 0.38). The single-bone fixation group had a significantly shorter mean operative time in comparison to both-bones plating (43.60 ± 6.21 vs. 88.60 ± 10.56 (min); p < 0.001). CONCLUSION: Single-bone ulna open reduction and plate fixation and casting are safe and had a significantly shorter operative time than both-bone fixation. However, single-bone ORIF had a higher risk radius re-angulation, alas clinically acceptable. Both groups had equally excellent functional outcomes, forearm ROM, and union rates with no complications or refractures. Long-term studies are required.

Donor site morbidity of calcaneal, distal tibial, and proximal tibial cancellous bone autografts in foot and ankle surgery. A systematic review and meta-analysis of 2296 bone grafts.

PURPOSE: This study aims to report on the safety and donor site morbidity of the distal lower extremity (calcaneal, proximal, and distal tibial) cancellous bone autografts. We summarized the findings in a comprehensive infographic illustration. We are unaware of any similar meta-analyses to date. METHODS: Following the PRISMA guidelines, two independent investigators searched MEDLINE (PubMed), EMBASE, SCOPUS, Google Scholar, and Cochrane databases in December 2020 using the following keywords and their synonyms: ("bone graft", "donor site morbidity", "calcaneal graft", "proximal tibia graft", and "distal tibia graft"). Besides, the reference lists from previous review articles were searched manually for eligible studies. The primary outcomes of interest were (1) chronic pain, (2) fracture, and (3) infection, whereas the secondary outcomes were (1) neurological complications, (2) sensory disturbance and hypertrophic scars, (3) other complications such as shoe-wear difficulties and gait disturbance. Inclusion criteria were: studies on complications and adverse events of lower extremity bone autografts (calcaneal, proximal tibial, and distal tibial bone autografts) reporting at least one of the desired outcomes. Studies not reporting any of the outcomes of interest or if the full text is not available in English were excluded. Studies reporting on bone marrow aspirate or autografts for non-orthopedic indications were also excluded. RESULTS: After the removal of duplicates, a total of 5981 studies were identified. After screening those records, 85 studies remained for full-text assessment. Out of those, 15 studies qualified for the meta-analysis with a total of 2296 bone grafts. Out of those grafts, 1557(67.8%) were calcaneal grafts, 625 (27.2%) were proximal tibial grafts, and 114 (5%) were distal tibial grafts. In calcaneal bone grafts, there were 28 cases of chronic pain [1.97%, CI:1.10-2.50%, I2 = 66%], 5 fractures [0.32%, CI: 0.10-0.60%,I2 = 0%], 20 sural neuritis [1.28%, CI:0.70-1.80%, I2 = 0%), and no wound infections. In proximal tibial grafts there were 13 cases of chronic pain [2.08%, CI: 1.01-3.2%, I2 = 34.5%], 1 fracture [0.16%, CI:0.10-0.50%, I2 = 0%], and 3 superficial wound infections [0.48%, CI: 0.10-1.01, I2 = 0%]. In the distal tibial grafts there were no cases of chronic pain or wound infections, 1 fracture [0.90%, CI: 0.80-2.6%, I2 = 0%], and 5 saphenous neuritis [4.5%, CI: 0.70-8.40%, I2 = 65%]. CONCLUSION: Calcaneal, distal tibial, and proximal tibial bone autografts are safe with a low rate of overall and major complications. We report an overall complication rate of 6.8%, which is less than half of that previously reported for iliac crest grafts. The authors recommend using distal lower extremity grafts for foot and ankle primary surgeries instead of iliac crest grafts when indicated. Clinical trials with a large sample size are required.

Locked intramedullary nailing provides superior functional outcomes and lower complication rates than plate fixation of distal fibula fractures. A systematic review and meta-analysis of comparative studies.

PURPOSE: This study aims to provide an updated systematic review and meta-analysis of comparative studies on the outcomes and complications of locked IMNs in comparison to ORIF using plates and screws, while avoiding limitations of similar published reviews. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, two independent team members electronically searched MEDLINE (PubMed), EMBASE, Google Scholar, SCOPUS, and Cochrane databases throughout May 2021 using the following keywords with their synonyms: "Ankle fracture fixation" AND "Open reduction and internal fixation", "locked intramedullary nail", or "complications". The primary outcomes were (1) functional outcomes, (2) complications, and (3) reoperation, while the secondary outcomes were: (1) union rate, and (2) cost. INCLUSION CRITERIA: comparative studies on outcomes and complications of plate open reduction and internal fixation (ORIF) vs. locked intramedullary nailing (IMN) of ankle fractures reporting at least one of the following parameters: functional outcomes, complications (infection, dehiscence, reoperation etc.), union, and cost. Studies reporting on non-locked intramedullary fibular nails were also excluded. RESULTS: After the removal of duplicates, a total of 1461 studies were identified. After screening those records, 63 studies remained for full-text assessment. Out of those, four comparative studies with a total of 262 ankle fractures met the inclusion criteria for this meta-analysis. The mean 12 months postoperative Olerud and Molander Ankle Scores (OMAS) were reported by two studies, with a statistically significant difference in favor of IMNs (MD= 6.72, CI: 3.77-9.67, p<0.001, I2= 94%). In the ORIF group, the overall complication rate was 39/134 (29.1%) vs. 10/128 (7.8%) in the IMN group, with a statistically significant difference in favor of the IMN group (RR=3.23, CI:1.71-6.11, p<0.001, I2=34%). In the ORIF group, the overall infection rate was 11/134 (8.2%), while there were no infections in the IMN group, with a statistically significant difference in favor of the IMN group (RR=8.05, CI:1.51-42.82, p=0.01, I2=0%). In the ORIF group, the overall reoperation rate was 10/134 (7.5%) while the overall reoperation rate was 6/128 (4.7%) in the IMN group, with no statistically significant difference between groups (RR=1.49, CI: 0.60-3.70, p = 0.39, I2=0%). CONCLUSION: Locked intramedullary nail fixation of distal fibula fractures could provide superior functional outcomes and lower complication rates in comparison to open reduction and plate fixation. Despite the high incidence of ankle fractures, the number of high-quality comparative studies remains limited in literature, especially on newer locked fibular nails, and large multicentric clinical trials are required before recommending locked IMNs as the new standard of care in distal fibula fractures.

Examining the relationships between early childhood experiences and adolescent and young adult health status in a resource-limited population: A cohort study.

BACKGROUND: Adolescence is a critical point in the realization of human capital, as health and educational decisions with long-term impacts are made. We examined the role of early childhood experiences on health, cognitive abilities, and educational outcomes of adolescents followed up from a longitudinal cohort study in Pakistan, hypothesizing that early childhood experiences reflecting poverty would manifest in reduced health and development in adolescence. METHODS AND FINDINGS: Adolescents/young adults previously followed as children aged under 5 years were interviewed. Childhood data were available on diarrhea, pneumonia, and parental/household characteristics. New data were collected on health, anthropometry, education, employment, and languages spoken; nonverbal reasoning was assessed. A multivariable Bayesian network was constructed to explore structural relationships between variables. Of 1,868 children originally enrolled, 1,463 (78.3%) were interviewed as adolescents (range 16.0-29.3 years, mean age 22.6 years); 945 (65%) lived in Oshikhandass. While 1,031 (70.5%) of their mothers and 440 (30.1%) of their fathers had received no formal education, adolescents reported a mean of 11.1 years of education. Childhood diarrhea (calculated as episodes/child-year) had no association with nonverbal reasoning score (an arc was supported in just 4.6% of bootstrap samples), health measures (with BMI, 1% of bootstrap samples; systolic and diastolic blood pressure, 0.1% and 1.6% of bootstrap samples, respectively), education (0.7% of bootstrap samples), or employment (0% of bootstrap samples). Relationships were found between nonverbal reasoning and adolescent height (arc supported in 63% of bootstrap samples), age (84%), educational attainment (100%), and speaking English (100%); speaking English was linked to the childhood home environment, mediated through maternal education and primary language. Speaking English (n = 390, 26.7% of adolescents) was associated with education (100% of bootstrap samples), self-reported child health (82%), current location (85%) and variables describing childhood socioeconomic status. The main limitations of this study were the lack of parental data to characterize the home setting (including parental mental and physical health, and female empowerment) and reliance on self-reporting of health status. CONCLUSIONS: In this population, investments in education, especially for females, are associated with an increase in human capital. Against the backdrop of substantial societal change, with the exception of a small and indirect association between childhood malnutrition and cognitive scores, educational opportunities and cultural language groups have stronger associations with aspects of human capital than childhood morbidity.

Return to sport following navicular stress fracture: a systematic review and meta-analysis of three hundred and fifteen fractures.

PURPOSE: This meta-analysis aims to provide updated evidence on the success rate, return to play (RTP) rate, time to RTP, and complications of operatively and conservatively managed navicular stress fractures (NSFs) as well as delays in diagnosis while avoiding limitations of previous similar studies. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, two independent team members electronically searched MEDLINE (PubMed), EMBASE, Google Scholar, SCOPUS, and Cochrane databases throughout February 2021 using the following keywords with their synonyms: "Navicular stress fracture," "return to play," and "athletes." The primary outcomes were (1) management success rate, (2) RTP rate, and (3) time to RTP. The secondary outcomes were (1) non-union, (2) time to diagnosis, (3) refracture, and (4) other complications. Inclusion criteria were clinical studies on NSFs reporting at least one of the desirable outcomes. Studies not reporting any of the outcomes of interest or the full text was not available in English, German, French, or Arabic were excluded. Case reports, case series with less than ten cases, and studies reporting exclusively on navicular non-union management were also excluded. The Newcastle-Ottawa scale was used for quality assessment while Review Manager (RevMan) Version 5.4 was used for the risk of bias assessment. Data were presented by type of treatment (surgical or conservative). If enough studies were present that were clinically and statistically homogeneous and data on them adequately reported, a meta-analysis was performed using a fixed-effects model. In case of statistical heterogeneity, a random-effects model was used. If meta-analysis was not possible, results were reported in a descriptive fashion. The need to explore for statistical heterogeneity was determined by an I2 greater than 40%. RESULTS: Eleven studies met the inclusion criteria with a total of 315 NSF. Out of those, 307 (97.46%) NSFs were in athletes. One hundred eight (34.29%) NSFs were managed operatively, while 207 (65.71%) NSFs were managed conservatively. Successful outcomes were reported in 104/108 (96.30%) NSF treated operatively with a mean success rate of 97.9% (CI: 95.4-100%, I2 = 0%). Successful outcomes were reported in 149/207 (71.98%) NSF treated conservatively, with a mean success rate of 78.1% (CI: 66.6-89.6%, I2 = 84.93%). Successful outcome differences were found to be significant in favor of operative management (OR = 5.52, CI: 1.74-17.48, p = 0.004, I2 = 4.6%). RTP was noted in 97/98 (98.98%) NSF treated operatively and in 152/207 (73.43%) NSF treated conservatively, with no significant difference between operative and conservative management (OR = 2.789, CI: 0.80-9.67, p = 0.142, I2 = 0%). The pooled mean time to RTP in NSF treated operatively was 4.17 months (CI: 3.06-5.28, I2 = 92.88%), while NSF treated conservatively returned to play at 4.67 months (CI: 0.97-8.37, I2 = 99.46%) postoperatively, with no significant difference between operative and conservative management (SMD = - 0.397, CI: - 1.869-1.075, p = 0.60, I2 = 92.24). The pooled mean duration of symptoms before diagnosis was 9.862 (3.3-123.6) months (CI: 6.45-13.28, I2 = 94.92%), reported in ten studies. Twenty (23.53%) refractures were reported after conservative management of 85 NSFs, while one (1.28%) refracture was reported after operative management of 78 NSFs, with a significant difference in favor of operative management (OR = 0.083, CI: 0.007-0.973, p = 0.047, I2 = 38.78%). CONCLUSION: Operative management of NSF provides a higher success rate, a lower refracture rate, and a lower non-union rate as compared to other non-operative management options. While not significant, there is a notable trend towards superior RTP rates and time to RTP following operative management. Therefore, we recommend operative fixation for all NSFs type I through III in athletes. Athletes continue to exhibit an alarmingly long duration of symptoms before diagnosis is made; a high index of suspicion must be maintained, therefore, and adjunct CT imaging is strongly recommended in the case of any work-up. Unfortunately, the published literature on NSFs remains of lower level of evidence and high-quality studies are needed.

Double versus triple arthrodesis for adult-acquired flatfoot deformity due to stage III posterior tibial tendon insufficiency: a prospective comparative study of two cohorts.

PURPOSE: The study aims to prospectively compare double and triple arthrodesis in terms of functional outcomes and deformity correction. To the best of our knowledge, this is the first prospective comparative study in the literature to date. METHODS: This is a prospective comparative cohort study carried out between May 2017 and May 2019. The study was approved by the IRB at Assiut University and done according to the Helsinki declaration. Patients with AAFD stage III aged between 15 and 40 years old were assigned to double arthrodesis or triple arthrodesis. The groups were prospectively followed for one year. Primary outcomes were union rates, AOFAS scores, and radiological parameters of deformity correction on AP and lateral plain radiographs. Secondary outcomes were operative time, time to union, and complications. The double arthrodesis was done through the medial approach, while the triple arthrodesis was done through dual medial and lateral approaches. The post-operative protocol was standardized for both groups. RESULTS: A total of twenty-three patients matched the inclusion criteria and provided their consent to participate in the study. Thirteen (all males) patients underwent double arthrodesis, while ten (nine males and one female) patients underwent triple arthrodesis. The mean age for double and triple arthrodesis was 20.15 ± 5.63 and 25.10 ± 8.36 years, respectively, and the mean follow-up lengths were 12.46 and 12.9 months, respectively. There were no statistically significant differences between both groups in age, gender, laterality, or duration of follow-up. There were no statistically significant differences between both groups in AOFAS hindfoot scores or radiographic parameters. All patients were available for the final follow-up evaluation. All patients in both groups achieved union by four months post-operatively. The mean time to union in the double and triple arthrodesis groups was 3.39 ± 0.65 vs. 3.31 ± 0.6 months, respectively, with no statistically significant differences (p = 0.77). The mean operative time was significantly shorter in the double arthrodesis group than the triple arthrodesis group, 55.77 ± 15.18 vs. 91.6 ± 24.14 min (p < 0.001), respectively. Both double and triple arthrodesis groups had a statistically significant improvement of the mean AOFAS hindfoot score post-operatively (71.46 ± 7.77 vs. 88.38 ± 3.66, p < 0.001) and (66.9 ± 7.69 vs. 85 ± 5.83, p < 0.001), respectively. In the double arthrodesis group, the mean calcaneal pitch angle increased from 11.46° pre-operatively to 19.34° (MD = 8.45°, p < 0.001). The mean Meary's angle improved from - 4.19 to 2.9° (MD = 7.32°, p < 0.001). Hibbs angle had a mean reduction of 6.45° post-operatively (p = 0.069). In the triple arthrodesis group, the mean calcaneal pitch angle improved from 10.06° pre-operatively to 17.49° post-operatively (MD = 7.12°, p < 0.001). The mean Meary's angle improved from - 4.72 to 2.29° (MD = 7.09°, p < 0.001). The mean Hibbs angle decreased from 153.07 to 142.32° (MD = 10.54°, p < 0.001). The double vs. triple arthrodesis groups had no statistically significant differences in AOFAS hindfoot score improvement (16.92 vs. 19.1, p = 0.44), respectively. The two groups had no statistically significant differences in the magnitude of correction of all the radiographic parameters. CONCLUSION: Double arthrodesis is an equally reliable surgical option for AAFD stage III for achieving union, improving the functional outcomes, and deformity correction as triple arthrodesis with a significantly shorter operative time in the former. The authors recommend double arthrodesis if the calcaneocuboid joint is unaffected.

Protein kinase CK2 impact on intracellular calcium homeostasis in prostate cancer.

Protein kinase CK2 plays multiple roles in cell function in normal and disease states. CK2 is elevated in numerous types of cancer cells, and CK2 suppression of apoptosis represents a key link to the cancer cell phenotype. CK2 regulation of cell survival and death involves diverse processes, and our previous work suggested that mitochondrial machinery is a key locus of this function. One of the earliest responses of prostate cells to inhibition of CK2 is a change in mitochondrial membrane potential, possibly associated with Ca2+ signaling. Thus, in the present work, we investigated early impact of CK2 on intracellular Ca2+ dynamics. Three prostate cancer (PCa) cell lines, PC3-LN4, C4-2B, and 22Rv1, were studied. PCa cells were treated with the CK2 small molecule inhibitors 4,5,6,7-tetrabrombenzotriazole and CX-4945 followed by analysis of Ca2+ levels in various cellular compartments over time. The results showed dose-dependent loss in cytosolic Ca2+ levels starting within 2 min and reaching maximal loss within 5-10 min. There was a concomitant increase in Ca2+ in the endoplasmic reticulum (ER) and mitochondrial compartments. The results suggest that inhibition of CK2 activity results in a rapid movement of Ca2+ out of the cytosol and into the ER and mitochondria, which may be among the earliest contributory factors for induction of apoptosis in cells subjected to inhibition of CK2. In cells with death-inducing levels of CK2 inhibition, total cellular Ca2+ levels dropped at 2 h post-treatment. These novel observations represent a potential mechanism underlying regulation of cell survival and death by CK2 activity.

Peroneal tendon dislocation in talus fracture and diagnostic value of fleck sign.

INTRODUCTION: Talus fractures are not uncommon and one of the serious fractures in the foot and ankle. Peroneal tendon dislocation is one of the commonly missed soft tissue injuries which may have significant impact on the outcomes including persistent pain and swelling. They have been reported to be associated with calcaneum as well as talus fractures. AIM: To report the incidence of peroneal tendon dislocation in talus fracture and the significance of fleck sign in the diagnosis of peroneal tendon dislocation. METHODS: We retrospectively reviewed 93 consecutive talus fractures in the period between 1/1/2011 to 1/11/2018. Inclusion criteria were: The patient underwent open reduction and internal fixation, had pre-operative CT scan that is available for review and three view ankle plain radiographs. Two independent authors review the radiographs for peroneal tendon dislocation, fleck sign and fracture classification, if any. Any dispute was resolved by the senior author.Patient records were reviewed for laterality, age, sex,mode of injury, associated injuries and operative interventions. 50 ankles met the inclusion criteria. 49 were males, mean age was 32.5 year and the predominant mode of injury was a fall from height. RESULTS: Peroneal tendon dislocation was found in ten patients out of 50 (20%). Risk of dislocation increased with severity of the fracture and neck fractures. Most of the dislocations were missed by surgeons and radiologist, and no additional procedures were done to address such an injury. The Fleck sign had a statistically significant correlation with peroneal tendons dislocations (p=.005) CONCLUSION: Peroneal tendons dislocation is associated with as high as 20% of talus fractures. The authors recommend carefully reviewing CT scans by surgeons and radiologists alike to avoid missing such injury and allow for appropriate surgical approach utilization. The Fleck sign is a highly specific radiographic sign that has a statistically significant correlation with PT dislocation and hence we recommend intra-operative assessment of peroneal tendons in patients with the fleck sign.

Preclinical Pharmacological Activities of Epigallocatechin-3-gallate in Signaling Pathways: An Update on Cancer.

Epigallocatechin gallate (EGCG) is the main bioactive component of catechins predominantly present in svarious types of teas. EGCG is well known for a wide spectrum of biological activity as an anti-oxidative, anti-inflammatory, and anti-tumor agent. The effect of EGCG on cell death mechanisms via the induction of apoptosis, necrosis, and autophagy has been documented. Moreover, its anti-proliferative and chemopreventive action has been demonstrated in many cancer cell lines. It was also involved in the modulation of cyclooxygenase-2, in oxidative stress and inflammation of different cell processes. EGCG has been reported as a promising target for plasma membrane proteins, such as epidermal growth factor receptor (EGFR). In addition, it has been demonstrated a mechanism of action relying on the inhibition of ERK1/2, p38 MAPK, NF-κB, and vascular endothelial growth factor (VEGF). EGCG and its derivatives were used in proteasome inhibition and they were involved in epigenetic mechanisms. In summary, EGCG is the most predominant and bioactive constituent of teas and it has a pivotal role in cancer prevention. Its preclinical pharmacological activities are associated with complex molecular mechanisms that involve numerous signaling pathways.

Ethnic differences in the receptors status of estrogen, progesterone and Her2/Neu among breast cancer women: A single institution experience.

OBJECTIVE: To evaluate the Ethnic Differences in Estrogen (ER), Progesterone (PR) and Her 2/neu receptors among Women with Breast Cancer at JPMC, the largest public sector tertiary care hospital in Karachi. METHODS: The study was conducted at the oncology ward, JPMC Karachi from 1st July 2017 to 31st December 2018. During this period, more than 500 women with breast cancer of different ethnicities visited the oncology ward, however 450 patients were included in the study, as only they had the complete reports on the receptors status and tumour histology. The data collected included tumour histology, grade, receptors status, age and ethnicity. Data was analyzed with SPSS version 20 using the Chi-Square Test to observe statistical differences in the receptors status of different ethnicities. RESULTS: Analysis of receptors status as per ethnicity showed that ER was proportionately more positive in Pushtoon patients at the rate of 28 (75.7%) as compared to Urdu Speaking 116 (60.4%), Punjabis 48 (60%), Sindhis 38(38.7%) and Balochis 26 (61.1%). Similarly, PR and Her-2/neu receptor were also higher in Pushtoons at the rate of 24 (64.9%) and 15 (40.5%) respectively. The behaviour of Triple Positivity was also more prominent in Pushtoons at the rate of 9 (24.3%) and the Pushtoons were also proportionately less likely to be Triple Negative at the rate 05 (13.5%) as compared to other ethnicities. All the results were statistically non significant (p values>0.05). CONCLUSIONS: In this study we observed a relatively higher expression of ER, PR and Her 2/neu Receptors in Pushtoons as compared to other ethnicities. Understanding the factors underlying these differences may provide further insight into the breast cancer aetiology in different populations.

Arthroscopic Bankart repair for the acute anterior shoulder dislocation: systematic review and meta-analysis.

BACKGROUND: The ideal treatment of acute anterior shoulder dislocation remains one of the topics that spark debate over the value of primary repair for the first-time anterior shoulder dislocation. The high rate of complications especially in young adults, such as recurrent instability, residual pain, and inability to return to sports, has led to the quest for an ideal management of such injuries. OBJECTIVE: In this meta-analysis, we compare between the immediate arthroscopic repair and conservative treatment of primary anterior shoulder dislocation as well as arthroscopic reconstruction of recurrent anterior shoulder dislocation. Outcome measures were failure rate (dislocation, subluxation, and instability) and revision rates. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched several database including PubMed, MEDLINE, EMBASE, Web of Science, Cochrane Library, and ClinicalTrials.gov through August 2017 to identify observational and experimental randomized controlled trials comparing the outcomes of immediate arthroscopic repair and conservative treatment of primary shoulder dislocations as well as arthroscopic reconstruction of recurrent dislocation. The primary outcome was failure rate, whereas, secondary outcomes were revision rate and functional outcomes. RESULTS: Out of the 710 studies identified, 12 were eligible for meta-analysis. The estimated pooled failure rate was 13.7% (7.7%-19.6%), whereas, the pooled revision rate was 7.1% (3.8%-10.4%) in immediate arthroscopic repair of primary shoulder dislocation. The odd ratio (OR) of failure and revision rates were significantly lower in arthroscopic repair of primary shoulder dislocation compared to conservative treatment (OR 0.103, 95% CI [0.052, 0.201]), (OR 0.217, 95% CI [0.078, 0.607]), respectively. The odd ratio (OD) of failure and revision rates were lower in arthroscopic repair of primary shoulder dislocation compared to arthroscopic reconstruction of the recurrent shoulder dislocation; however, the difference was statistically insignificant (OR 0.423, 95% CI [0.117, 1.522]) and (OR 0.358, 95% CI [0.044, 2.920]) respectively. CONCLUSION: The outcome of immediate arthroscopic repair of primary anterior shoulder dislocation is superior and encouraging with significant reduction in failure and revision rates compared to conservative treatment. Nevertheless, the failure and revision rates are statistically insignificant compared to arthroscopic reconstruction of recurrent dislocation. Hence, there is evidence to support immediate arthroscopic repair option for primary anterior shoulder dislocations over conservative treatment in young active patients, in order to reduce the risk of failure and revision rates. However, the evidence is inconclusive compared to arthroscopic reconstruction of recurrent dislocation.

The evaluation ofefficacy and safety of Cough (EMA) granules used for upper respiratory disorders.

Ivy leaf is used for the treatment of respiratory diseases with the intensive mucus formation, respiratory infections, and irritating cough coming from the common cold. Conferring to clinical trials, the efficacy, and tolerability of ivy leaf is good. The main compounds accountable for biological activity are triterpene and saponins. Ivy leaves show convulsive/antispasmodic, anti-inflammatory, antimicrobial, analgesic, anthelmintic and anti-thrombin activity. Not only ivy but also marshmallow and mustard seeds are used for these indications. This study was conducted to evaluate the efficacy and safety of Cough (EMA; European Medicines Agency) granules used for upper respiratory disorders. This clinical trial was conducted on 150 patients, out of which 75received the Cough (EMA) granules and 75received the placebo. The age range of patients was 3 years to above 15 years. The sample paired t-test was applied to evaluate the significant level. Cough (EMA) granules were found effective in the treatment of cough, cold, and flu symptoms. The new treatment Cough (EMA) granules were safe and well tolerated in patient at given specific age group. The study recommends that Cough (EMA) granules can be used effectively in the treatment of upper respiratory tract infection.

Autologous mesenchymal stromal cell transplantation for spinal cord injury: A Phase I pilot study.

BACKGROUND AIMS: Mesenchymal stromal cell (MSC) transplantation has immerged as promising therapeutic approach to treat spinal cord injury (SCI). In this pilot study, we investigated the safety of intrathecal injection of autologous bone marrow-derived MSCs in nine patients with SCI. METHODS: Patients with complete SCI at the thoracic level were divided into two groups: chronic (>6 months, group 1) and sub-acute SCI (<6 months, group 2), according to time elapsed since injury. MSCs were isolated by density gradient separation of autologous bone marrow harvested from the iliac crest. Cells were cultured in a Good Manufacturing Practice-compliant facility to produce clinical scale dose. After quality control testing, MSCs were injected back to patients by intrathecal injection. Safety was defined as absence of adverse event and side effects after 1 month after receiving the injection. RESULTS: Six patients had chronic SCI with a median duration of 33 months since date of injury (range: 10-55 months), and three patients were in sub-acute phase of disease. Each patient received two or three injections with a median of 1.2 × 10(6) MSCs/kg body weight. No treatment-related adverse event was observed during median follow-up of 720 days (range: 630-826 days) in group 1 and 366 days (range: 269-367 days) in group 2, respectively. DISCUSSION: This pilot study demonstrated that autologous MSCs can be safely administered through intrathecal injection in spinal cord injury patients. Further investigation through randomized, placebo-controlled trials is needed.

Examination of CK2α and NF-κB p65 expression in human benign prostatic hyperplasia and prostate cancer tissues.

Protein kinase CK2 plays a critical role in cell growth, proliferation, and suppression of cell death. CK2 is overexpressed, especially in the nuclear compartment, in the majority of cancers, including prostate cancer (PCa). CK2-mediated activation of transcription factor nuclear factor kappa B (NF-κB) p65 is a key step in cellular proliferation, resulting in translocation of NF-κB p65 from the cytoplasm to the nucleus. As CK2 expression and activity are also elevated in benign prostatic hyperplasia (BPH), we sought to increase the knowledge of CK2 function in benign and malignant prostate by examination of the relationships between nuclear CK2 and nuclear NF-κB p65 protein expression. The expression level and localization of CK2α and NF-κB p65 proteins in PCa and BPH tissue specimens was determined. Nuclear CK2α and NF-κB p65 protein levels are significantly higher in PCa compared with BPH, and these proteins are positively correlated with each other in both diseases. Nuclear NF-κB p65 levels correlated with Ki-67 or with cytoplasmic NF-κB p65 expression in BPH, but not in PCa. The findings provide information that combined analysis of CK2α and NF-κB p65 expression in prostate specimens relates to the disease status. Increased nuclear NF-κB p65 expression levels in PCa specifically related to nuclear CK2α levels, indicating a possible CK2-dependent relationship in malignancy. In contrast, nuclear NF-κB p65 protein levels related to both Ki-67 and cytoplasmic NF-κB p65 levels exclusively in BPH, suggesting a potential separate impact for NF-κB p65 function in proliferation for benign disease as opposed to malignant disease.