Heme Detoxification Protein (PfHDP) is essential for the hemoglobin uptake and metabolism in Plasmodium falciparum.

Hemoglobin degradation is crucial for the growth and survival of Plasmodium falciparum in human erythrocytes. Although the process of Hb degradation has been studied in detail, the mechanisms of Hb uptake remain ambiguous to date. Here, we characterized Heme Detoxification Protein (PfHDP); a protein localized in the parasitophorus vacuole, parasite food vacuole, and infected erythrocyte cytosol for its role in Hb uptake. Immunoprecipitation of PfHDP-GFP fusion protein from a transgenic line using GFP trap beads showed the association of PfHDP with Hb as well as with the members of PTEX translocon complex. Association of PfHDP with Hb or Pfexp-2, a component of translocon complex was confirmed by protein-protein interaction and immunolocalization tools. Based on these associations, we studied the role of PfHDP in Hb uptake using the PfHDP-HA-GlmS transgenic parasites line. PfHDP knockdown significantly reduced the Hb uptake in these transgenic parasites in comparison to the wild-type parasites. Morphological analysis of PfHDP-HA-GlmS transgenic parasites in the presence of GlcN showed food vacuole abnormalities and parasite stress, thereby causing a growth defect in the development of these parasites. Transient knockdown of a member of translocon complex, PfHSP101 in HSP101-DDDHA parasites also showed a decreased uptake of Hb inside the parasite. Together, these results advocate an interaction between PfHDP and the translocon complex at the parasitophorus vacuole membrane and also suggest a role for PfHDP in the uptake of Hb and parasite development. The study thus reveals new insights into the function of PfHDP, making it an extremely important target for developing new antimalarials.

Special emphasis on bone health management in prostate cancer patients: a prospective longitudinal study

ABSTRACT Introduction: Use of androgen deprivation therapy (ADT) in carcinoma prostate (CaP) has deleterious effect on bone mineral density (BMD) leading to increase incidence of osteoporosis and skeletal-related events. We evaluated bone health status and impact of bone-directed therapy (BDT) and ADT on BMD in these patients from Jan 2015-Dec 2018. Materials and Method: Baseline bone health was assessed using Tc-99 MDP Bone scan/ DEXA scan for patients on ADT. Monthly zoledronic acid (ZA) was given to high-risk candidates (T-score ≤2.5 or previous hip/vertebral fracture) or Skel et al. metastatic patients who were receiving ADT. Baseline and follow-up (at 12-months) BMD using DEXA scan at various sites (spine, femur total, femur neck and radius) and subjective improvement in bony pain using Numeric Pain Rating Score after administration of ZA were compared. Results: A total of 96-patients of locally advanced and metastatic prostate cancer receiving ADT with or without BDT were included in the study cohort. Mean age of presentation was 68.4±15.61 years. Median serum PSA was 32.2±13.1ng/mL. There was significant improvement in mean BMD (T-score) in 64-patients post ZA therapy at 12-months (at femoral total, femoral neck and spine; 0.95, 0.79 and 0.68, respectively) (p <0.05) while there was significant deterioration in mean BMD at 12-months (at spine, femoral neck and femoral total; −0.77, −0.55 and −0.66, respectively) in 32 patients who did not receive ZA and were on ADT (p <0.05). Pain scores significantly decreased in patients after 12-months of ZA use (−2.92±2.16, p <0.01). Conclusion: Bone-directed therapy (Zoledronic acid) leads to both subjective and objective improvement in bone health of prostate cancer patients on ADT.

Identifying and ranking the driving forces of social insurance by analytical hierarchy process: evidence from India.

Imperfections in the private market increase the scope of social insurance worldwide. Social insurance is designed to provide protection against heterogeneous risks. In a welfare state, consumer's demand for social insurance arises from the need for optimum policy coverage. Likewise, government intervention facilitates the insurance market by minimizing the effect of imperfect information and moral hazard. Designing cost and benefits of a policy, assessing the required level of risk to be taken and selecting integrated services (for example, medical care) are among the salient roles of the supplier. The present paper tries to find out the main drivers for social insurance in India. For this purpose, we have applied the Analytic Hierarchy Process (AHP) to determine the most important alternative among the different alternatives. The model consists of nine criteria and three alternatives. The results show that the consumer's demand is on the top of the hierarchy which signifies that the optimum policy coverage must be given due to consideration for mass administration of social insurance programs. The findings are important for policymakers in order to address consumer's needs so that enrollments in the insurance policies can be enhanced. The contribution of the study significantly includes the determination of a new set of study variables along with the application of the AHP methodology.

Prospective randomized comparison of repairing vesicovaginal fistula with or without the interposition flap: Result from a tertiary care Institute in Northern India.

OBJECTIVE: Assessment of results of repairing vesicovaginal fistula (VVF) with or without the use of interposition flaps. MATERIAL AND METHODS: This prospective randomized study was conducted between January 2012 to December 2017 in the Department of Urology, King George's Medical University, Lucknow, India. Obstetric and gynecological simple fistula of ≤4 cm were included for evaluation. Those with complex or complicated fistula or fistula due to malignancy were excluded. Patients were divided into two groups (group 1 and group 2) depending upon route of repair i.e., transvaginal or transabdominal, respectively, as per the characteristics and location of the fistula. These two groups of patients were randomized into two subgroups (1A, 1B and 2A, 2B) based on the inclusion or omission of the interposition flap during fistula repair. Perioperative and postoperative parameters (blood loss, mean operating time, hospital stay, and requirement of analgesics) and success rates of fistula repair were compared. All complications that occurred in the postoperative period till the last follow-up appointment were recorded. The Clavien-Dindo Classification was used to stratify the complications. RESULTS: Fifty-seven patients underwent transvaginal repair in group 1 (29 with Martius flap: group 1A; 28 without Martius flap: group 1B), while 69 patients underwent transabdominal repair in group 2 (35 with interposition flap: group 2A; 34 without flap: group 2B). Blood loss, mean operating time, hospital stay, and the requirement of analgesics were comparable between each subgroup-1A versus 1B and 2A versus 2B, respectively. The overall success rate of repair across all groups was 96.04% (121/126). The success rate was 93.1% in transvaginal repair with Martius flap versus 96.43% in transvaginal repair with no flap (p=1.0). Success rate was 97.1% in transabdominal repair with an omental flap versus 97.06% in without an omental flap (p=1.0). Mean follow-up period was 39.6 months (range: 6-68 months). Out of 29 patients with Martius flap interposition, 9 (31.03%) of them reported a significantly reduced sensation on the labia majora. Of these 9 patients, 5 reported numbness while the remaining 4 experienced pain as compared to the patients in subgroup IB, who did not report any altered sensation in the labia. (p=0.0019). CONCLUSION: The success rates are similar in simple VVF repair (fistula size less than 4 cm) irrespective of the use of interposition flaps. However, overall morbidities following repair with the interposition flap are higher when compared with repair without interposition flap, either by the transvaginal or by the transabdominal route.

Prospective randomized comparison between transperitoneal laparoscopic pyeloplasty and retroperitoneoscopic pyeloplasty for primary ureteropelvic junction obstruction.

BACKGROUND AND OBJECTIVES: To compare laparoscopic transperitoneal versus retroperitoneoscopic pyeloplasty for primary ureteropelvic junction obstruction in a prospective randomized manner and assess overall results with long-term follow-up. METHODS: In this prospective study, from 2008 to 2012, 112 cases of primary ureteropelvic junction obstruction were randomized in a 1:1 ratio into 2 groups. Group I included patients who underwent transperitoneal laparoscopic pyeloplasty, and group II consisted of patients who underwent retroperitoneoscopic laparoscopic pyeloplasty. Demographic and clinical characteristics and postoperative and operative data were collected and analyzed. The statistical analysis was performed with the Fisher exact test, χ2 test, and Mann-Whitney U test for independent groups, and P<.05 was considered statistically significant. RESULTS: The total operative time and intracorporeal suturing time were significantly higher in group II than in group I (P<.001). The visual analog scale score for pain on postoperative day 1 and the requirement for tramadol were significantly higher in group I than in group II (P=.004). The hospital stay and the rate of temporary ileus were significantly greater (P<.036 and P<.02, respectively) in group I than in group II. The success rate of transperitoneal laparoscopic pyeloplasty versus retroperitoneoscopic laparoscopic pyeloplasty was 96.4% versus 96.6% with a mean follow-up period of 30.75±4.85 months versus 30.99±5.59 months (P<.88). CONCLUSION: Transperitoneal laparoscopic pyeloplasty is associated with significantly greater postoperative pain, a higher tramadol dose, a higher rate of ileus, and a longer hospital stay in comparison with retroperitoneoscopic laparoscopic pyeloplasty. Although the operative time for retroperitoneoscopic laparoscopic pyeloplasty is significantly longer, the success rate remains the same for both procedures.

Transperitoneal versus retroperitoneal laparoscopic ureterolithotomy: a prospective randomized comparison study.

PURPOSE: We compared laparoscopic transperitoneal and retroperitoneal ureterolithotomy approaches, and determined whether one technique is superior to the other. MATERIALS AND METHODS: In this prospective randomized study from January 2009 to May 2012, 48 patients with proximal or mid ureteral stones underwent transperitoneal laparoscopic ureterolithotomy or retroperitoneal laparoscopic ureterolithotomy. The randomization occurred on a 1:1 basis. Groups 1 and 2 consisted of patients who underwent transperitoneal laparoscopic ureterolithotomy and retroperitoneal laparoscopic ureterolithotomy, respectively. Demographic and clinical characteristics as well as postoperative data were collected and analyzed. Statistical analysis was performed with SPSS® version 15.0 using the Fisher exact and Mann-Whitney U tests with p <0.05 considered statistically significant. RESULTS: The difference in visual pain analog score and mean tramadol requirement on days 1 and 2 between the 2 groups was statistically significant, and was higher in group 1 (p <0.05). Postoperative hospital stay and paralytic ileus rates were significantly higher in group 1 (p <0.05). The differences in total operative time and intracorporeal suturing time between the 2 groups were not statistically significant. However, successful stone removal was equal in the 2 groups. CONCLUSIONS: For proximal or mid ureteral large and impacted stones, transperitoneal laparoscopic ureterolithotomy is significantly associated with pain, greater tramadol requirement, ileus and longer hospital stay than retroperitoneal laparoscopic ureterolithotomy. However, successful stone removal remains the same in both groups.

Hair dye poisoning in Bundelkhand region (prospective analysis of hair dye poisoning cases presented in Department of Medicine, MLB Medical College, Jhansi).

AIMS OF STUDY: Hair dye (Paraphenylene di-amine, PPD) poisoning has high morbidity and mortality and its incidence has increased dramatically in the past 4 years. A prospective study was planned to assess the clinical profile and outcome with different treatment approaches. MATERIAL AND METHODS: The material comprised of 1020 cases admitted in Medicine Department of MLB Medical College, Jhansi, U.P. from July 2004 to March 2009. Out of 1020 cases 697 cases were of stone hair dye poisoning and 323 cases were of other branded hair dyes (powdered form containing less amount of Paraphenylene diamine). Diagnosis was made solely on the basis of the history given by cases/attendant and symptoms of neck swelling, black coloured urine and muscular pain. The cases were thoroughly studied for different complications (renal, hepatic and cardiac etc) and were treated accordingly. RESULTS: Out of 1020 cases studied, majority were females in the age group of 15-45 yrs (n=734) while the rest were males. A total of 244 (23.92%) cases expired during treatment. Neck swelling, respiratory distress and whole body muscular pain were most common symptoms at presentation, oliguria, chest pain, palpitation, presyncope/syncope, pain in abdomen, nausea with vomiting and dysphagia were other common symptoms. CONCLUSION: Paraphenylene diamine is highly toxic. Cases who consumed up to 10 gm of PPD usually survived if they presented to hospital within 4 hour of dye ingestion. Severe edema of face, neck and floor of mouth, renal failure and myocarditis were poor prognostic factors. No deaths occurred in cases of Branded Hair dye ingestion.

Distal myocardial protection with intracoronary beta blocker when added to a Gp IIb/IIIa platelet receptor blocker during percutaneous coronary intervention improves clinical outcome.

OBJECTIVE: The present study tested the hypothesis that intracoronary (IC) propranolol improves clinical outcomes with percutaneous coronary intervention (PCI) when used with background Gp IIb/IIIa receptor blockade. BACKGROUND: We have previously shown that administration of a relatively large weight-based IC dose of the beta blocker propranolol before PCI decreases the incidence of post-PCI myocardial infarction (MI) and improves short- and long-term outcome. It has previously been shown that administration of a Gp IIb/IIIa receptor blocker decreases post-PCI MI and improves short- and long-term clinical outcome. METHODS: Patients undergoing PCI (n = 400) were randomized in a prospective double-blind fashion to IC propranolol (n = 200) or placebo (n = 200) with eptifibatide administered to all the patients. Myocardial isoform of creatine kinase was measured during the first 24 hr and clinical outcomes at 30 days and 1 year. RESULTS: MI after PCI was seen in 21.5% of placebo and 12.5% of propranolol patients (relative risk reduction 0.42; 95%CI 0.09, 0.63; P = 0.016). At 30 days, the composite end point of death, post-procedural MI, urgent target lesion revascularization, or MI after index hospitalization occurred in 22.5% of placebo vs. 13.5% of propranolol patients (risk reduction 0.43; 95%CI 0.08, 0.65; P = 0.018). Similar results were observed at 1 year with adverse outcomes in 21.5% of propranolol and 32.5% of placebo patients (P = 0.01). CONCLUSION: IC propranolol administration with the background Gp IIb/IIIa receptor blockade significantly reduces the incidence of post-PCI MI and improves the short- and long-term clinical outcome when compared with a Gp IIb/IIIa blocker alone.

Echocardiographic aspects of hiatal hernia: A review.

It was realized 20 years ago that the sonographic appearance of a diaphragmatic hernia could simulate a left atrial mass. Many papers have appeared on this topic since then, but they mainly consist of single case reports. Clinical symptoms due to cardiac compression by the hernia are uncommon but may occur if the hernia is very large; such patients have presented with episodes of syncope or dyspnea, typically after a large meal. Sonographers, cardiologists, gastroenterologists, and internists are generally not yet aware that sonographic presentations can be varied and are often perplexing. These include the combination of hiatal hernia with gastroesophageal reflux demonstrable in the subcostal view, and hiatal hernia in patients with ascites.

Diffuse locally invasive lipomatosis of the pericardium.

The chest radiographic, echocardiographic (transthoracic and transesophageal), MRI, CT and cardiac catheterization findings in a 72-year-old patient with extensive pericardial lipomatosis are presented. Diastolic pressures in the left heart were elevated. The massive lipomatous mass was partially resected surgically with good symptomatic relief. Histologically the neoplasm consisted of mature non-malignant adipose tissue. Cushing's Syndrome was absent.