Polymeric micelles and cancer therapy: an ingenious multimodal tumor-targeted drug delivery system.

Since the beginning of pharmaceutical research, drug delivery methods have been an integral part of it. Polymeric micelles (PMs) have emerged as multifunctional nanoparticles in the current technological era of nanocarriers, and they have shown promise in a range of scientific fields. They can alter the release profile of integrated pharmacological substances and concentrate them in the target zone due to their improved permeability and retention, making them more suitable for poorly soluble medicines. With their ability to deliver poorly soluble chemotherapeutic drugs, PMs have garnered considerable interest in cancer. As a result of their remarkable biocompatibility, improved permeability, and minimal toxicity to healthy cells, while also their capacity to solubilize a wide range of drugs in their micellar core, PMs are expected to be a successful treatment option for cancer therapy in the future. Their nano-size enables them to accumulate in the tumor microenvironment (TME) via the enhanced permeability and retention (EPR) effect. In this review, our major aim is to focus primarily on the stellar applications of PMs in the field of cancer therapeutics along with its mechanism of action and its latest advancements in drug and gene delivery (DNA/siRNA) for cancer, using various therapeutic strategies such as crossing blood-brain barrier, gene therapy, photothermal therapy (PTT), and immunotherapy. Furthermore, PMs can be employed as "smart drug carriers," allowing them to target specific cancer sites using a variety of stimuli (endogenous and exogenous), which improve the specificity and efficacy of micelle-based targeted drug delivery. All the many types of stimulants, as well as how the complex of PM and various anticancer drugs react to it, and their pharmacodynamics are also reviewed here. In conclusion, commercializing engineered micelle nanoparticles (MNPs) for application in therapy and imaging can be considered as a potential approach to improve the therapeutic index of anticancer drugs. Furthermore, PM has stimulated intense interest in research and clinical practice, and in light of this, we have also highlighted a few PMs that have previously been approved for therapeutic use, while the majority are still being studied in clinical trials for various cancer therapies.

Impact of Foliar Application of ZnO and Fe3O4 Nanoparticles on Seed Yield and Physio-Biochemical Parameters of Cucumber (Cucumis sativus L.) Seed under Open Field and Protected Environment vis a vis during Seed Germination.

Nutritionally rich cucumber seeds remain in demand in the agricultural, health and cosmetic sectors as they are essential for a successful crop stand establishment and seed-based products. However, the production of cucumber seeds is impeded by source limitation and nutrient deficiency. The foliar application of micronutrients can supplement this deficiency and overcome the physiological setback. An experiment was undertaken to compare the impacts of the foliar application of Fe and Zn, as nanoparticles and fertilizers, on the yield and seed quality of cucumber under open and protected environments. A foliar spray of nano-ZnO (ZnNPs) and nano-Fe3O4 (FeNPs) at 100, 200 and 300 mg L-1, as well as ZnSO4 and FeSO4 as fertilizer (0.5%), was conducted at the vegetative stage and pre- and post-flowering stages. The NPs had a greater efficacy in an open field than in the protected (naturally ventilated poly house) environment. The application of both NPs increased seed yield (51.7-52.2%), total chlorophyll content (15.9-17.3%) and concentration of Zn and Fe in the fruit and the seed, by 2.0-58.5% and 5.0-30.5%, respectively. A significant increase in starch, soluble proteins, soluble sugars and oil content was observed in the seeds from the NP treated plants. NP treatment also enhanced the germination-related parameters, such as percent germination (16.8-17.0%), rate of germination (18.0-22.2%) and seedling vigor (59.8-72.6%). The biochemical characterization showed a significant improvement in the seed water uptake and the activity of hydrolytic enzymes (amylase and protease) in the germinating seed. The involvement of reactive oxygen species (superoxide anion and hydrogen peroxide) and antioxidant enzymes (Superoxide dismutase, Catalase and Peroxidase) in the germination process was indicated by an increase in their activities in the seeds from NP treated plants. Hence, the study proposes the potential benefit of the foliar application of 300 mg L-1 ZnNPs and 200 mg L-1 FeNPs at crucial stages of plant growth to improve the yield and seed quality in cucumbers.

Efficacy and Safety of Topical Solution of Diperoxochloric Acid for Neuropathic Diabetic Foot Ulcer: Results from a Phase 3, Multicentre, Randomized, Active-controlled, Parallel-group Study.

Diabetic foot ulcer (DFU), if untreated, accounts for lower-limb amputations affecting patients' quality-of-life. Diperoxochloric acid (DPOCL) is known to heal DFU by its antibacterial and fibroblast stimulating activity. This was a phase 3, multicentre, randomized, double-blind, active-controlled, parallel-group study conducted to evaluate the efficacy and safety of topic solution of DPOCL compared with isotonic sodium chloride solution (ISCL). Adult patients with type 1 or 2 diabetes with random blood glucose levels of <250 mg/dL, with ≤ than three full-thickness foot ulcers were enrolled. Primary efficacy endpoint was complete wound closure and secondary was wound surface area. Adverse events were analyzed as safety endpoint. Of 311 enrolled patients, 289 were randomized 1:1 to DPOCL (139) and ISCL (150) treatment (10-weeks [8-Visits]). Percentage of patients with complete wound closure at visit-8, were significantly higher (P = .0156) in DPOCL arm (76% [105/139]) compared to ISCL (62% [93/150]) arm. At end-of-study, mean wound surface area in DPOCL arm (0.639 cm2) was significantly lower (P = .0209) compared to ISCL (0.818 cm2) arm. One death was reported in control arm which was not considered as treatment-related. No important safety finding were observed. Results indicate that, DPOCL can be considered as effective and safe treatment option for DFU compared to ISCL, although future confirmatory studies are warranted.

Systematic Review of Comparison of use of Ultrasonic Scalpel Versus Conventional Haemostatic Techniques in Performing Thyroid Surgery.

Haemostasis during any surgical procedure is fundamental for attaining a positive patient outcome. Safe thyroid surgery requires meticulous attention for careful control of bleeding and safe guarding important structures like recurrent laryngeal nerve. Many methods such as ligation and suturing, electro ligation sealing, coagulation, and ultrasonic coagulation have been put to use for achieving haemostasis. The objective of this systemic review was to compare and review the surgical outcomes between harmonic (ultrasonic) scalpel and conventional ligature techniques in performing thyroid surgery. The systematic review was performed in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement and checklist with a total of 11 studies selected for qualitative analysis. The statistical software Review Manager 5.4.1 provided by the Cochrane Collaboration was used for performing the analysis on the two groups. It was concluded that the use of harmonic scalpel for thyroid surgery is useful for reducing operative time, postoperative pain, drainage volume and transient hypocalcemia, hence can be a reliable and a safe tool compared to conventional techniques often used for surgery.

Rare presentation of isolated hydatid disease of the breast.

Isolated hydatid disease of the breast is a rare condition, possessing a diagnostic dilemma for the clinicians. Hydatid disease is common in endemic areas affecting most commonly the liver and lungs. Other organs rarely involved are the kidney, bone and brain. It is caused by the parasite Echinococcus granulosus, widely spread by cattle and sheep. Humans are the accidental host for this organism. We present a similar case of isolated hydatid cyst of the breast, which was diagnosed preoperatively and managed successfully.

A randomised controlled trial of Lichtenstein repair with Desarda repair in the management of inguinal hernias.

BACKGROUND: Ever since the advent of mesh hernioplasty with low recurrence rates, surgeons have turned a blind eye towards its devastating mesh related complications. Consequently, the quest for the best hernia surgery, that is as effective as the mesh repair but lacks its complications, continues. OBJECTIVES: The present study was carried out to compare the results of the Lichtenstein repair with the Desarda repair in the treatment of inguinal hernias. METHODS: A total of 77 patients with 87 hernias were randomly allocated into two groups to undergo either the Desarda repair (Group I, 39 patients with 45 hernias) or the Lichtenstein repair (Group II, Control, 38 patients with 42 hernias). 3 patients didn't complete the follow-up and were excluded from analysis. Finally, 40 hernias were analyzed in the Lichtenstein group and 44 in the Desarda group. RESULTS: After a 6-month follow-up period it was found that neither of the two groups had any recurrence. The incidence of chronic inguinodynia was much higher in the Lichtenstein group as compared to Desarda group. The pain scores, mean operating time, mean time to return to work and analgesic requirement was much lower with the Desarda repair as compared to Lichtenstein repair. CONCLUSION: Desarda repair was found to be as effective as the Lichtenstein repair in terms of recurrence and better in terms of chronic inguinodynia, complications and post operative pain scores. Desarda repair requires a significantly shorter operating time. The economic burden of this repair is much less compared to mesh repair.

The Role of Antibiotic Prophylaxis in Lichtenstein Repair of Primary Inguinal Hernia: A Prospective Double-Blind Randomized Placebo-Controlled Trial.

OBJECTIVE: The objective is to study the role of antibiotic prophylaxis, if any, in the prevention of wound infection after open mesh repair of primary inguinal hernias. MATERIALS AND METHODS: Patients coming to outpatient department for open mesh repair of inguinal hernia were randomized into the placebo group and antibiotic group, a total of 150 patients were enrolled in the study. Follow-up was done up to 1 month to look for any evidence of surgical site infection using the criteria of Centers for Disease Control on wound infection. RESULTS: Twelve patients in the antibiotic group and nine patients in the placebo group were found to have evidence of surgical site infection. This difference was found to be insignificant with P = 0.14. Three patients in the placebo group developed deep surgical site infection but on analysis, this difference was also found to be insignificant with P = 0.122.None of these patients required mesh removal. CONCLUSION: The result of the present study suggests that the use of prophylactic antibiotics during mesh repair of primary inguinal hernias does not give any extra protection from infections. Multicenter meta-analysis is required to give definite guidelines regarding the use of prophylactic antibiotics.

Spontaneous Rectus Sheath Hematoma Masquerading as Acute Abdomen. A Case Report.

A 60-year old female presented to the emergency department with complaints of acute abdominal pain and lump in the right upper abdomen. Physical examination revealed a large tender abdominal lump in the right hypochondrium, extending up to the right lumbar region. Further examination revealed that the lump was parietal and not intra-abdominal. Contrast Enhanced Computed Tomography abdomen was done and a right rectus sheath hematoma was diagnosed. No predisposing factor for spontaneous rectus sheath hematoma was identified. Following an unsuccessful conservative treatment, the patient underwent surgical drainage of rectus sheath hematoma with ligation of bleeding vessels. She fully recovered, with an uneventful postoperative period and without recurrence.

Prevalence and risk factors of soil-transmitted helminth infections in school age children (6-14 years) - A cross-sectional study in an urban resettlement colony of Delhi.

BACKGROUND: Soil-transmitted helminth (STH) infections have adverse physical and mental effect, especially in preschool (3-6 years) and school-age children (6-14 years). They are associated with socio-behavioral factors of poverty and poor personal and community hygiene. OBJECTIVES: To determine the prevalence, intensity, and the type of helminths infection harbored by the school age children (6-14 years) and to examine the relationship between STH infection and their potential risk factors and associated variables. METHODS: This cross-sectional study was conducted from January to December 2016 among 250 school age children residing in an urban resettlement colony of East Delhi. Data were collected using a semistructured interview schedule. Stool sample was tested using the Kato Katz technique. Data were analyzed in SPSS software version 16, and multivariable regression analysis was done to calculate the odds of various risk factors. RESULTS: The prevalence of STH was found to be 54.8%, and majority (85.3%) of Ascaris and all Trichuris infections were of light intensity. Multivariable logistic regression analysis confirmed that children having poor handwashing behavior in school, irregular handwashing before eating, having pica, and lack of de-worming had higher odds of having STH infection. CONCLUSION: The prevalence of STH in the study area is substantially high, and the findings suggest that besides mass de-worming strategy, behavior change, and improvement in hygiene are required to control STH.

Cholera outbreak investigation, Bhadola, Delhi, India, April-May 2018.

BACKGROUND: In the Gangetic plains of India, including Delhi, cholera is endemic. On 10 May 2018, staff at the north Delhi district surveillance unit identified a laboratory-confirmed cholera outbreak when five people tested positive for Vibrio cholerae O1 Ogawa serotype in Bhadola. We investigated to identify risk factors and recommend prevention measures. METHODS: We defined a case as ≥3 loose stools within 24 h in a Bhadola resident during 1 April-29 May 2018. We searched for cases house-to-house. In a 1 : 1 unmatched case control study, a control was defined as an absence of loose stools in a Bhadola resident during 1 April-29 May 2018. We selected cases and controls randomly. We tested stool samples for Vibrio cholerae by culture. We tested drinking water for fecal contamination. Using multivariable logistic regression we calculated adjusted ORs (aORs) with 95% CIs. RESULTS: We identified 129 cases; the median age was 14.5 y, 52% were females, 27% were hospitalized and there were no deaths. Symptoms were abdominal pain (54%), vomiting (44%) and fever (29%). Among 90 cases and controls, the odds of illness were higher for drinking untreated municipal water (aOR=2.3; 95% CI 1.0 to 6.2) and not knowing about diarrhea transmission (aOR=4.9; 95% CI 1.0 to 21.1). Of 12 stool samples, 6 (50%) tested positive for Vibrio cholerae O1 Ogawa serotype. Of 15 water samples, 8 (53%) showed growth of fecal coliforms. CONCLUSIONS: This laboratory-confirmed cholera outbreak associated with drinking untreated municipal water and lack of knowledge of diarrhea transmission triggered public health action in Bhadola, Delhi.

Spontaneous Gastric Necrosis: A Rare Presentation of Invasive Mucormycosis in an Immunocompetent Adult.

Spontaneous gastric perforations are usually seen in patients with untreated peptic ulcer disease. Mucormycosis, an uncommon, opportunistic, life-threatening fungal infection, rarely causes gastric perforation in immunocompetent adults. Here, we present a case of young female who was admitted to hospital for acute pain abdomen and distension with 5 days history of fever. She was operated and was found to have multiple perforations in the stomach with transmural necrosis. Despite adequate surgical excision and intravenous amphotericin B, patient succumbed to sequelae of infection.

An outbreak of acute skin and soft tissue infections including necrotizing fasciitis in Kalwala village, India, 2018: Public health implications for the lymphatic filariasis elimination program.

BACKGROUND: A cluster of 15 acute skin and soft tissue infections (SSTIs), including two cases of necrotizing fasciitis, reported in July 2018 from Kalwala village, led us to investigate and describe their epidemiology and to provide recommendations. METHODS: Cases, defined as localized painful swelling and redness in Kalwala residents from 1 December 2017 to 20 August 2018, were identified from hospital records and house-to-house surveys. We conducted an unmatched case-control study to identify risk factors for severity. We cultured wound samples and environmental samples from wound-dressing stations. RESULTS: We identified 36 cases (median age: 55 [range 17-80] y; 78% male), village attack rate 1% (36/4337) and no deaths. In 34 cases (94%), lower limbs were involved. Lymphatic filariasis (LF) was a common predisposing condition (67%). Comorbidities (diabetes or hypertension) (OR=9; 95% CI 2.0 to 41.1), poor limb hygiene (OR=16; 95% CI 2.8 to 95.3) and poor health-seeking behavior (OR=5; 95% CI 1.6 to 30.8) were associated with severity. All seven wound samples and 8/11 samples from wound-dressing stations showed atypical polymicrobial growth (Pseudomonas, Proteus, Klebsiella, Escherichia coli and Clostridium). CONCLUSION: The outbreak of SSTIs among older males with LF was due to secondary bacterial infections and severity was associated with comorbidities, poor hygiene and health-seeking behavior, and likely contamination during wound-dressing. The LF elimination program managers was alerted, programmatic interventions were scaled up, home/facility-based morbidity and comorbidity management was facilitated and the outbreak was rapidly contained.

Impact of nonpharmacological interventions on COVID-19 transmission dynamics in India.

BACKGROUND: As of May 4, 2020, India has reported 42,836 confirmed cases and 1,389 deaths from COVID-19. India's multipronged response included nonpharmacological interventions (NPIs) like intensive case-based surveillance, expanding testing capacity, social distancing, health promotion, and progressive travel restrictions leading to a complete halt of international and domestic movements (lockdown). OBJECTIVES: We studied the impact of NPI on transmission dynamics of COVID-19 epidemic in India and estimated the minimum level of herd immunity required to halt it. METHODS: We plotted time distribution, estimated basic (R0) and time-dependent effective (Rt) reproduction numbers using software R, and calculated doubling time, the growth rate for confirmed cases from January 30 to May 4, 2020. Herd immunity was estimated using the latest Rtvalue. RESULTS: Time distribution showed a propagated epidemic with subexponential growth. Average growth rate, 21% in the beginning, reduced to 6% after an extended lockdown (May 3). Based on early transmission dynamics, R0was 2.38 (95% confidence interval [CI] =1.79-3.07). Early, unmitigated Rt= 2.51 (95% CI = 2.05-3.14) (March 15) reduced to 1.28 (95% CI = 1.22-1.32) and was 1.83 (95% CI = 1.71-1.93) at the end of lockdown Phase 1 (April 14) and 2 (May 3), respectively. Similarly, average early doubling time (4.3 days) (standard deviation [SD] = 1.86) increased to 5.4 days (SD = 1.03) and 10.9 days (SD = 2.19). Estimated minimum 621 million recoveries are required to halt COVID-19 spread if Rtremains below 2. CONCLUSION: India's early response, especially stringent lockdown, has slowed COVID-19 epidemic. Increased testing, intensive case-based surveillance and containment efforts, modulated movement restrictions while protecting the vulnerable population, and continuous monitoring of transmission dynamics should be a way forward in the absence of effective treatment, vaccine, and undetermined postinfection immunity.

A community-wide acute diarrheal disease outbreak associated with drinking contaminated water from shallow bore-wells in a tribal village, India, 2017.

BACKGROUND: In 2016, India reported 709 acute diarrheal disease (ADD) outbreaks (> 25% of all outbreaks). Tribal populations are at higher risk with 27% not having accessibility to safe drinking water and 75% households not having toilets. On June 26, 2017 Pedda-Gujjul-Thanda, a tribal village reported an acute diarrheal disease (ADD) outbreak. We investigated to describe the epidemiology, identify risk factors, and provide evidence-based recommendations. METHODS: We defined a case as ≥3 loose stools within 24 h in Pedda-Gujjul-Thanda residents from June 24-30, 2017. We identified cases by reviewing hospital records and house-to-house survey. We conducted a retrospective cohort study and collected stool samples for culture. We assessed drinking water supply and sanitation practices and tested water samples for faecal-contamination. RESULTS: We identified 191 cases (65% females) with median age 36 years (range 4-80 years) and no deaths. The attack-rate (AR) was 37% (191/512). Downhill colonies (located on slope of hilly terrains of the village) reported higher ARs (56%[136/243], p < 0.001) than others (20%[55/269]). Symptoms included diarrhea (100%), fever (17%), vomiting (16%) and abdominal pain (13%). Drinking water from five shallow bore-wells located in downhill colonies was significantly associated with illness (RR = 4.6, 95%CI = 3.4-6.1 and population attributable fraction 61%). In multi-variate analysis, drinking water from the shallow bore-wells located in downhill colonies (aOR = 7.9, [95% CI =4.7-13.2]), illiteracy (aOR =6, [95% CI = 3.6-10.1]), good hand-washing practice (aOR = 0.4, [95%CI = 0.2-0.7]) and household water treatment (aOR = 0.3, [95%CI = 0.2-0.5]) were significantly associated with illness. Two stool cultures were negative for Vibrio cholerae. Heavy rainfall was reported from June 22-24. Five of six water samples collected from shallow bore-wells located in downhill colonies were positive for faecal contamination. CONCLUSION: An ADD outbreak with high attack rate in a remote tribal village was associated with drinking water from shallow downhill bore-wells, likely contaminated via runoff from open defecation areas after heavy rains. Based on our recommendations, immediate public health actions including repair of leakages at contaminated water sources and alternative supply of purified canned drinking water to families, and as long-term public health measures construction of house-hold latrines and piped-water supply initiated.

Isolated Fungal Balls in Urinary Bladder Presenting as Acute Retention of Urine.

A 52-year-old male presented to surgery emergency with acute retention of urine. Patient was relieved in the emergency setting by catheterization and bladder irrigation. Urine was sterile; however, microscopy revealed field full of RBCs (>50/high-power field) and pus cells (>20/hpf). Cystoscopy revealed fungal balls in the urinary bladder which upon histopathological examination showed Aspergillus species. Patient was managed with systemic voriconazole and bladder wash with diluted povidone iodine. Predisposing factors diabetes mellitus and benign prostatic hyperplasia were medically managed, and patient recovered well. This case stresses the importance of considering isolated fungal urinary infections in predisposed individuals.

Online Medical Teaching in COVID-19 Era: Experience and Perception of Undergraduate Students.

Introduction: Rapid emergence of COVID-19 as pandemic has affected the life of almost every human being and has changed the way people used to interact. It has also affected medical education and clinical training, and forced medical schools to switch over to online mode of teaching. The aim of this study was to learn about the experience and perception of undergraduate students regarding online teaching. Methods: This is a cross sectional observational study conducted among the undergraduate students of Hamdard Institute of Medical Sciences and Research, New Delhi, India. A validated electronic questionnaire with nine questions was sent to 177 students as Google FormsTM. Responses from 161 students were received and analyzed using SPSS software. Results:The majority of students were satisfied with the frequency, organization, content and preparedness of classes. Half of students were neither satisfied with the amount of syllabus covered nor online teaching method. Among various teaching methods, live online lectures were most common and they were also preferred by the majority of students. Most students want hybrid or blended teaching in the post COVID-19 era. Conclusion: Online or e-teaching alone is not preferred by the majority of students. Lack of interpersonal interaction is the most likely reason for this. Hybrid or blended teaching holds the future of medical education as it is more student friendly and efficient.

Pre-sternal thyroid swellings: a case of rare aberrant site recurrence and review of literature.

BACKGROUND: Thyroid swellings enlarge caudally into the mediastinum behind the sternum. Pre-sternal swelling of thyroid origin is very rare. We present our case of pre-sternal thyroid swelling which was albeit a surprisingly rare site of papillary thyroid carcinoma recurrence and review of pre-sternal thyroid swellings reported till date. CASE SUMMARY: A 60 year old female presented with a painless, progressive swelling on the anterior part of the chest for the past 2 years. A 15 cm × 8 cm vertically aligned, non tender, well defined swelling was present on the pre-sternal region, with consistency ranging from soft to firm. The swelling was fixed to the underlying tissues and a fixed level IV lymph node was palpable on the right side. Ultrasonography revealed a large mass of 15 × 7 cm with multiple cystic areas. Fine needle aspiration cytology was inconclusive twice. Patient had undergone a total thyroidectomy for papillary carcinoma 10 years back. Computed tomography findings revealed a large 15 × 6.6 × 7 cm lobulated, pre-sternal, soft tissue lesion with solid & cystic components. The mass was infiltrating the right sided strap muscles and sternocleidomastoid. FNAC was inconclusive and thyroid scan could not pick up any activity in the mass. Henceforth a PET scan was done that showed increased FDG uptake by the lesion and the level IV lymph node. The patient underwent wide excision of the mass with right functional neck dissection, along with removal with both sternal head of sternocleido-mastoid, the strap muscles and the surrounding fascia. Histopathology confirmed papillary thyroid carcinoma. Patient received post-operative radioactive iodine ablation and is healthy with no recurrence up to 30 months of follow up. DISCUSSION: The mechanisms for pre-sternal thyroid swelling are not understood due to paucity of cases. The mechanisms proposed are invasion of strap muscles and cervical linea alba and tumor cells spread anterior to sternum, truly ectopic thyroid tissue, de novo carcinogenesis in the embryonal remnants like the thyro-thymic residues, sequestered thyroid tissue which grows later or migration of thyroid cells, incomplete clearance at the time of primary surgery or intraoperative seeding. CONCLUSION: Pre-sternal region masses of thyroid origin are very rare. A proper work up, suspicion for thyroid mass and array of tests will be required to come to a provisional diagnosis. Since the masses reported in literature were primarily malignant, any such mass may be treated on lines of malignancy with radical surgery.

Intravesical gossypiboma: our experience and the need for stringent checklist and training!

We present our experience of two cases: one of a 28-year-old male patient who presented with recurrent episodes of urinary tract infection (UTI) with passage of pus flakes in urine and a history of open cystolithotomy about 10 months ago. The second patient was a 26-year-old woman who underwent bladder exploration for a retained Double-J stent about 10 months ago and presented with recurrent UTI. The first case was treated with open surgery and in the second case, the gauze piece was retrieved endoscopically.