Analyzing Interaction of Rhodacyanine Inhibitor 'MKT-077' with Plasmodium falciparum HSP70s.

INTRODUCTION: MKT-077 and its derivatives are rhodacyanine inhibitors that hold potential in the treatment of cancer, neurodegenerative diseases and malaria. These allosteric drugs act by inhibiting the ATPase action of heat shock proteins of 70 kDa (HSP70). MKT-077 accumulates in the mitochondria and displays differential activity against HSP70 homologs. METHODS: The four Plasmodium falciparum HSP70s (PfHSP70) are present in various subcellular locations to perform distinct functions. In the present study, we have used bioinformatics tools to understand the interaction of MKT-077 at the ADP and HEW (2-amino 4 bromopyridine) binding sites on PfHSP70s. Our molecular docking experiments predict that the mitochondrial and endoplasmic reticulum PfHSP70 homologs are likely to bind MKT-077 with higher affinities at their ADP binding sites. RESULTS: Binding analysis indicates that the nature of the identified interactions is primarily hydrophobic. We have also identified specific residues of PfHSP70s that are involved in interacting with the ligand. CONCLUSION: Information obtained in this study may form the foundation for the design and development of MKT-077-based drugs against malaria.

Heat current magnification in classical and quantum spin networks.

We investigate heat current magnification (CM) due to asymmetry in the number of spins in two-branched classical as well as quantum spin systems that are kept between two heat baths at different temperatures. We study the classical Ising-like spin models using Q2R and Creutz cellular automaton dynamics. We show that just the difference in the number of spins is not enough and some other source of asymmetry like unequal spin-spin interaction strengths in the upper and lower branches is required for heat CM. We also provide a suitable physical motivation for CM along with ways to control and manipulate it. We then extend this study to a quantum system with modified Heisenberg XXZ interaction and preserved magnetization. Interestingly, in this case, just the asymmetry in the number of spins in the branches is enough to achieve heat CM. We observe that the onset of CM is accompanied by a dip in the total heat current flowing through the system. We then discuss how the observed CM characteristics can be attributed to the intersection of nondegenerate energy levels, population inversion, and atypical magnetization trends as a function of the asymmetry parameter in the Heisenberg XXZ Hamiltonian. Finally we use the concept of ergotropy to support our findings.

Hyponatremia an indicator of complicated appendicitis in children: Starship experience.

BACKGROUND: Timely preoperative recognition of children with complicated appendicitis allows for planning and effective management. The aim of this study was to evaluate hyponatremia, an objective biochemical marker, as a predictor of complicated appendicitis. METHODS: A retrospective review of 1283 paediatric patients (≤15 years) who underwent acute appendicectomy from January 2016 to December 2020 (5-year period) was performed. Complicated appendicitis was defined by intraoperative findings of; macroscopic perforation, free pus, gangrene, faecal contamination or intraabdominal abscess. Comparison groups consisted of patients with complicated appendicitis, patients with uncomplicated appendicitis and patients with presumed appendicitis who went on to have no appendicitis on histology (no appendicitis group). Preoperative hyponatremia was defined as serum sodium <135 mmol/L. RESULTS: Of the 1283 children; 35% (443/1283) had complicated appendicitis, 54% (690/1283) had uncomplicated appendicitis and 12% (150/1283) had no appendicitis. Rates of hyponatremia were much greater in the complicated group (31.4%; 139/443) than in the uncomplicated group (3.8%; 26/690) (p < 0.0001) or the no appendicitis group 10.7% (16/150) (p < 0.0001). The no appendicitis group had higher rates of hyponatremia than the uncomplicated group (p = 0.001), an unexpected finding. The receiver operating characteristic curve for diagnosis of complicated appendicitis versus uncomplicated appendicitis, using a cut-off serum sodium of <135 mmol/L will identify complicated appendicitis with sensitivity 31.4% and specificity of 95.7% (area under the curve of 0.76). CONCLUSION: Hyponatremia is a discriminating predictor of complicated appendicitis in a paediatric population.

Heat rectification by two qubits coupled with Dzyaloshinskii-Moriya interaction.

We investigate heat rectification in a two-qubit system coupled via the Dzyaloshinskii-Moriya (DM) interaction. We derive analytical expressions for heat currents and thermal rectification and provide possible physical mechanisms behind the observed results. We show that the anisotropy of DM interaction in itself is insufficient for heat rectification, and some other form of asymmetry is needed. We employ off-resonant qubits as the source of this asymmetry. We find the regime of parameters for higher rectification factors by examining the analytical expressions of rectification obtained from a global master equation solution. In addition, it is shown that the direction and quality of rectification can be controlled via various system parameters. Furthermore, we compare the influence of different orientations of the DM field anisotropy on the performance of heat rectification. Finally, we investigate the possible interplay between quantum correlations and the performance of the quantum thermal rectifier. We find that asymmetry in the coherences is a fundamental resource for the performance of the quantum thermal rectifier.

Side predilection in congenital anomalies of the kidney, urinary and genital tracts.

BACKGROUND: There appear to be various patterns of sidedness with relation to the common urogenital malformations observed in pediatric urology. The objective of this statistical review was to synthesize this data and to assess if these patterns are significant. MATERIALS AND METHODS: Eighteen urogenital conditions were investigated and for each condition the five largest studies that noted laterality were included. The sidedness of each condition was then analysed for statistical significance. RESULTS: Three conditions had a statistically significant higher proportion on the right side: palpable undescended testis (63%, p = 0.0002), inguinal hernia (59%, p = 0.0001) and hydrocele (60%, p = 0.003). Three conditions were significantly more common on the left side: impalpable undescended testis (59%, p = 0.0008), renal agenesis (54%, p = 0.02) and vesico-ureteric junction obstruction (71%, p < 0.0001) while both pelvi-ureteric junction obstruction (62%, p = 0.09) and absent vas deferens (61%, p = 0.11) were trending towards significance. CONCLUSIONS: Various urogenital malformations display a predilection for one side. Proximal malformations tend to be more frequently seen on the left side, where as inguinoscrotal malformations are more frequently observed on the right. There is an increasing body of literature regarding aetiological factors for these conditions. However, our current understanding of the pathophysiology of these conditions does not completely explain this pattern of observation.

Is hook diathermy safe to dissect the mesoappendix in paediatric patients? A 10-year experience.

BACKGROUND: Laparoscopic appendicectomy is one of the most commonly performed abdominal surgical procedures in children, with many different techniques used to isolate and control the appendiceal artery. Previous studies have looked into the utility of different methods of mesoappendix dissection, however these have been predominantly small-scale studies performed on adults. AIM: The current study aimed to assess the safety and efficacy of 'hook' diathermy as a sole means of mesoappendix dissection in children under 15 years of age undergoing laparoscopic appendicectomy. METHODS: Retrospective review of hospital database and electronic clinical notes of children aged under 15 who underwent laparoscopic appendicectomy at Starship Children's Hospital between 1 January 2007-31 December 2016. RESULTS: During the study period, 2,793 children had appendicectomy using hook diathermy to dissect the mesoappendix. No children required blood transfusions or return to theatre for bleeding. There were 103 intra-operative complications related to the use of hook diathermy (3.7%), including one case that required conversion to open for bleeding. CONCLUSION: Dissection of the mesoappendix using hook diathermy is a safe, quick and effective method during laparoscopic appendicectomy, with low complication and conversion to open rates.

Anterior abdominal wall defects managed at a tertiary maternal-fetal medicine service in New Zealand: What counselling advice can we offer parents?

BACKGROUND: Anterior abdominal wall defects, including gastroschisis and omphalocoele, are common fetal anomalies. The management remains complicated, and their diagnosis may lead to significant parental distress. Effective parental counselling may impact on parental perceptions of the defect and help guide pregnancy management. AIMS: Using contemporary data, we aimed to describe clinical outcomes of patients with gastroschisis or omphalocoele in order to provide information for clinicians to assist in parental counselling. MATERIALS AND METHODS: We followed a case-series of patients with anterior abdominal wall defects referred to our regional Maternal Fetal Medicine services from 2011 to 2016. Outcomes of interest antenatally included details of diagnosis, associated anomalies and outcomes of pregnancy and postnatally included the nature of surgical repair, hospital stay and secondary complications until initial discharge. RESULTS: Eighty babies with gastroschisis were referred antenatally, and 72 were liveborn. Forty-nine babies with omphalocoele were referred antenatally, and 24 were liveborn. One further neonate with omphalocoele was postnatally diagnosed. Seventy-one neonates with gastroschisis progressed to operation, 30 developed complications post-surgery, and 68 survived until initial discharge. Twenty-two neonates with omphalocoele progressed to surgery, only two developed complications, and 21 survived until initial discharge. Eight of the surviving neonates with omphalocoele had associated structural abnormalities. The median hospital stay was 27 and eight days for gastroschisis and omphalocoele, respectively. CONCLUSION: Neonates with gastroschisis can have complex postnatal periods. Omphalocoele is associated with high antenatal mortality, especially in the presence of associated abnormalities; however, surviving neonates may have uneventful postnatal periods.

Re-presentations and recurrent events following initial management of the acute paediatric scrotum: a 5-year review.

BACKGROUND: Previous reviews report relatively low rates of post-operative complications for acute scrotal exploration. The aim of this study was to evaluate the re-presentation to hospital in boys with previous acute scrotal pathology, reviewing contralateral symptoms, post-operative complications, testicular torsion following fixation and failure of conservative management of testicular appendage (TA) torsion. METHODS: All boys under 16 years presenting to our unit with an acute scrotum from January 2008 to December 2012 (5-year period) were identified. A retrospective review of clinical records was performed. RESULTS: A total of 683 boys presented over this 5-year period, with an overall re-presentation rate of 10%. Seventeen (25%) re-presentations were metachronous. Post-operative complication rate was 2.2%. Testicular torsion rate following orchiopexy was 0.3% (1/292). Thirty-three percent of those managed conservatively for TA torsion returned with ongoing pain; 80% underwent scrotal exploration on return. Eight boys returned following excision of a torted TA with contralateral torted TA confirmed, accounting for 2.6% (8/308) of boys with a torted TA at first presentation. This gives a number-needed-to-treat of 39 for bilateral scrotal exploration and prophylactic excision of contralateral non-torted TA, to prevent one boy from returning to hospital with a metachronous presentation. CONCLUSION: Further prolonged follow-up is needed to adequately assess recurrence rates of testicular torsion following orchiopexy to validate routine orchiopexy. Post-operative complication rates equal that of the return rate for a contralateral torted TA; this needs to be considered in proceeding to bilateral scrotal exploration on finding a torted TA at initial presentation.

Paediatric pelvic fractures: Starship Hospital experience.

AIM: Pelvic fractures constitute between 0.3% and 4% of all paediatric injuries, with a mortality rate up to 25%. This study aims to review the experience with pelvic fractures at Starship Children's Hospital and demonstrate its role as a marker of severe trauma. METHODS: A retrospective review of children with pelvic fractures managed at our institution in the 20-year period between July 1995 and May 2015 was performed. The search identified 179 consecutive children admitted with a pelvic fracture. Data fields collected included patient details, mechanisms of injury, investigations performed, length of hospital stay, management and complications. Data was also collected on Injury Severity Score (ISS), Glasgow coma scale (GCS), transfusion requirements and details of associated injuries (both orthopaedic and non-orthopaedic). RESULTS: Median age was eight years (IQR 5-12 years) with 65% boys. The median Injury Severity Score (ISS) was 9 (IQR 4-22). Pedestrian-motor vehicle injuries were most common at 46% of cases, followed by passengers injured in motor vehicle accidents accounting for 23% (n=41). Associated injuries were present in 68% (n=122) of patients, with other orthopaedic fractures (42%, n=75) and thoracic injuries (33%, n=59) most common. Management of pelvic fractures was primarily non-operative, with only 7% (n=13) requiring operative intervention. In comparison, operative procedures for associated injuries were much more common and were required in 38% (n=68) of cases. CONCLUSION: Pelvic fractures represent an important marker for severe trauma. Patterns of paediatric pelvic fractures reported by other studies around the world are very similar. Understanding the patterns in which pelvic fractures and their associated injuries occur and the outcome of treatment is fundamental to the establishment of effective preventative, diagnostic and therapeutic interventions.

Paediatric testicular tumours in a New Zealand centre.

AIM: This is a 12-year, single-centre retrospective review of paediatric testicular tumours and review of the world literature on paediatric testicular tumours. The aim was to identify presenting features, the range of pathology and management of such tumours in comparison with other published series. METHODS: The hospital's pathology database was searched for all testicular and paratesticular tissue submitted for patients younger than 16 years of age during the 12-year study period January 2000 to December 2011, and patients with testicular tumours identified. A detailed review of clinical records was then completed and summary statistics calculated. RESULTS: There were 33 tumours and 22 (66.7%) were malignant. The most common tumour was mature teratoma. No tumours presented with a twisted gonad. The mean incidence per year was 2.75 cases. This is comparable to other reported series worldwide (median 1.92, range 1.7-6.3). CONCLUSION: Testicular tumours in children are rare. In our centre, mature teratoma was the most common tumour, and malignant testicular tumours did not present with torsion. Our experience in managing gonadal tumours is similar to that published by major centres for paediatric surgery across the world. There is scope to develop the practice of testis-sparing surgery.

Age at referral for undescended testes: has anything changed in a decade?

AIM: Undescended testis (UDT) affects 1-6% of males and is one of the most common disorders in paediatric surgery.Updated consensus guidelines now recommend surgical management of UDT by 18 months. We compare the age at referral and subsequent timing of orchiopexy with data published from 1996-1998 at our institution, prior to the advent of updated guidelines. METHODS: A retrospective review of all patients undergoing an orchiopexy for UDT from 2014 to 2016 was conducted. The age at time of first referral, first outpatient review and age at date of surgery were recorded. Calculations were made for time between referral and clinic visit (T-1) and between clinic visit and surgery (T-2). Data are reported as median (range). RESULTS: In the 2014-2016 group (n=216), the median age at time of referral was 5.3 (range 0-182) months. Following referral, children were seen in the clinic at a median interval 1.84 (T-1: range 0.16-17) months. The median interval between the clinic visit and operation was 2.95 (T-2: range 0-30.7) months. The median age at time of surgery was 12.6 (range 4.6-191.3) months. Compared to the data from 1996-1998 (n=325), there was a drop in the median ages both at time of referral (23 months vs 5.3) and at time of operation (38.8 months vs 12.6). In this cohort, 66% (n=143) of boys had surgery before eighteen months of age. The median times between referral and clinic visit (T-1: 1.7 months vs 1.84) and between clinic and operation (T-2: 3.3 months vs 2.95) were essentially unchanged. CONCLUSION: Our second snapshot in time (2014-2016) shows improvements in median age at referral (under six months) and age at time of operation (at 12.6 months) when compared to the older snapshot (1996-1998). These timings are more in keeping with recommendations for orchiopexy.

Enterobius vermicularis and its role in paediatric appendicitis: protection or predisposition?

BACKGROUND: E nterobius vermicularis is one of the most common parasitic infections of the gastrointestinal tract, and has been shown to infest up to 28% of children worldwide. The role of E . vermicularis in acute appendicitis has previously been questioned, with some studies identifying infection as a precursor for inflammation of the appendix, with others refuting such a link. METHODS: A retrospective review was conducted of all appendices received for histological analysis at our unit from January 2002 to December 2011 (10-year period), removed in the course of acute appendicectomy in children aged 3 to 15 years. Appendices were categorized by degree of inflammation and infestation with E . vermicularis. RESULTS: Appendicectomy for clinical suspicion of acute appendicitis was performed in 2923 patients, 1694 (58%) male, median age 11.6 years. E . vermicularis was present in 4% of appendices; 25% of which showed concurrent acute inflammation. E . vermicularis infestation was more common in females (F : M 76% versus 24% of inflamed appendices and 66.7% versus 33.3% for non-inflamed appendices). European individuals showed higher representation in the E . vermicularis group than the total study population (79% versus 53% respectively). CONCLUSION: E . vermicularis was found to be more common in females and those of European descent. Seventy-seven percent of patients with E . vermicularis did not have concurrent acute inflammation of the appendix on histological examination. The question remains as to whether infestation is protective of inflammation or whether infestation causes appendiceal colic and subsequent appendicectomy of a non-inflamed appendix, thereby protective of the morbidity of acute appendicitis.

Megacystis Microcolon Intestinal Hypoperistalsis Syndrome: Case Reports and Discussion of the Literature.

Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a rare intestinal dysmotility condition that also involves a dilated urinary bladder. It was believed to be an autosomal recessive condition, but genetic studies have suggested possibly an autosomal dominant inheritance pattern. Prenatal diagnosis can be challenging, but MRI and amniotic fluid/digestive fluid studies may be complementary investigations to improve diagnostic accuracy. Prognosis of MMIHS is generally poor and treatment is mostly supportive. To date, bowel transplantation remains the only viable treatment to restore bowel motility. Here we present two additional cases to contribute towards the scant literature on this condition.

Paediatric ovarian lesions--the experience at Starship Children's Hospital, New Zealand.

AIM: To review the experience of paediatric ovarian masses at Starship Children's Hospital (Auckland, New Zealand). Primarily to assess the range of pathology, the presenting features, and the surgical management of these lesions. METHODS: A search of the hospital surgical pathology database was carried out to identify patients less than 16 years in whom ovarian tissue was submitted for pathological analysis during the 12 year period from January 2000 to December 2011. A retrospective review of the medical records was carried out. RESULTS: 244 ovarian masses in 219 patients were identified. 99 of these were neoplastic with 19 (7.8%) being malignant and an additional four (1.6%) borderline malignant lesions (borderline epithelial tumours). Mature cystic teratoma was the commonest neoplastic lesion (55.6%). Patients who presented with acute abdominal pain were more commonly found to have non-neoplastic lesions than neoplastic lesions (71.5% vs 46.9%, p<0.0001), and those that presented with a palpable mass were more commonly found to have a neoplastic lesion (24.0% vs 3.3%, p<0.0001). Laparoscopic surgery was performed in 41.6% of all patients. Ovary conserving surgery was performed in 56.6% of all patients, though only 32.3% of patients with neoplastic lesions. CONCLUSION: This study provides important insight into the range of ovarian pathology encountered in a New Zealand paediatric population. Most of the ovarian lesions in paediatric age groups are benign. Ovarian sparing surgery is recommended. In cases of ovarian torsion, malignancy in this series and in the literature is less than 2%. This review highlights that paediatric surgical units have vast experience to deal with ovarian pathology in paediatric age groups.

Duration of postoperative intravenous antibiotics in childhood complicated appendicitis: a propensity score-matched comparison study.

INTRODUCTION: Postoperative antibiotics complement surgery in managing childhood-complicated appendicitis. However, there is limited evidence to guide clinicians on appropriate duration of therapy. A comparison cohort study was performed to determine whether tailoring duration of inpatient intravenous (IV) antibiotic therapy to patient response, assessed using a set of clinical criteria, leads to shortened hospital length of stay (LOS) without compromising patient outcomes. PATIENTS AND METHODS: Over a 6-month period, 47 children (aged 5-14 years) with complicated appendicitis were treated with postoperative IV antibiotics until each satisfied a set of bedside clinical parameters suggesting resolved intraperitoneal infection (core temperature < 38°C for 24 hours, tolerated two consecutive meals, mobilizing independently, requiring only oral analgesia). Complicated appendicitis was defined as the presence of generalized peritonitis, appendiceal perforation or gangrene, and/or abscess. Postoperative recovery parameters were prospectively recorded and compared with those of 47 historical control patients, matched by propensity scores, who received 5 days minimum of postoperative IV antibiotics. Sample size was determined by a priori power calculation based on reduction in LOS. Severity of postoperative complications was graded using the Clavien-Dindo system. RESULTS: Study group variables were comparable including patient demographics, duration of presenting symptoms, severity of presenting disease, preoperative antibiotics received, length of operation, seniority of primary surgeon, surgical approach taken, and intraoperative findings. The prospective cohort had a significantly shorter median LOS compared with the historical control cohort (5 vs. 6 nights, p = 0.010) while readmission rates and the incidence and severity of complications were similar, including incidence of postoperative intra-abdominal infections (6 vs. 8 cases, p = 0.562). CONCLUSION: Using bedside clinical parameters indicative of resolved intraperitoneal infection to tailor duration of postoperative IV antibiotics for children with complicated appendicitis shortens LOS without apparent compromise to patient outcomes.

Evaluation of the BladderScan(®) in estimating bladder volume in paediatric patients.

OBJECTIVE: To evaluate the reliability of estimates of bladder volume (BV) in children with the BladderScan BVI 9400 (BS) compared with the volume obtained at catheterization (CV). MATERIALS AND METHODS: BV was measured using the BS in 50 children (age range 6 weeks-14 years) who required urinary catheter placement during surgery or urodynamic studies. BS measurements were taken prior to catheter insertion. BV was compared with CV. RESULTS: BS volumes ranged from 0 to 513 mL (mean = 79 mL, median = 34 mL) and CV from 0 to 500 mL (mean = 81 mL, median = 31 mL). There was high correlation between the BS and CV measures (rho = 0.96). The mean difference between BS and CV volumes was -2.1 mL (SD 21). Where the CV ≤ 100 mL the BS volumes ranged from 0 to 84 mL (mean = 74 mL, median = 30 mL) and the CV from 0 to 88 mL (mean = 76 mL, median = 25 mL) (rho = 0.89). The mean difference = 0.5 mL (95% limits of agreement ± 23 mL). In a small sample of 12 children <36 months, correlation between BS and CV volumes was not as strong with rho = 0.82. CONCLUSIONS: Overall the BladderScan showed a high correlation with catheter volume and there was good clinical agreement between the measures.

Carcinoid tumours of the appendix in children in Auckland, New Zealand: 1965-2008.

AIMS: Carcinoid tumours (CT) of the appendix are rare in children. The study aims to review paediatric CT of the appendix in Auckland and conduct a literature review. METHOD: Retrospective review of all CT of the appendix at the Auckland paediatric hospital from 1965 until 2008. Patients were identified from the Auckland Laboratory Pathology Department database. Patient charts and histopathological slides were reviewed when available. RESULTS: 47 children had a histologically confirmed CT of the appendix (34 females, 12 males). Mean age 12.3 years (7-15 years). Mean tumour diameter 0.83 cm (range 0.1 cm-2.3 cm). 55% tumour diameter <1 cm. Two patients had tumour diameters >2 cm. Extent of invasion known in 38 patients. Four within appendiceal submucosa, 11 into muscularis, 15 into serosa and 8 cases tumour extended to mesoappendix. Suspected appendicitis was the indication for surgery in each case. 44 patients had appendicectomy only, 3 patients had right hemicolectomy with residual tumour in one specimen. Literature search revealed 88 studies of which 11 case series of CT of the appendix in children were compared to our own study. CONCLUSION: CT of the appendix in children are uncommon. Most will be cured by appendicectomy only. Recurrence and metastatic disease are rare. Mesoappendiceal invasion is not an absolute indication for further surgery.

Syringocoele of the bulbourethral duct with additional lower genito-urinary anomalies.

The ultrasonographic (US) appearance of a syringocoele of the bulbourethral (Cowper) duct, with correlative urethrocystoscopic images, is demonstrated. An infant boy, 5 weeks of age, who presented with E. coli infection of the urinary tract also had bilateral hydroureteronephrosis, small bilateral simple ureterocoeles, and posterior urethral valve leaflets.

Primary school children: access to toilets.

AIM: Most children are continent of urine by the time they are in primary school. Balanced micturition and paradoxically dysfunctional voiding (DV) are acquired behaviour. Children need easy access to toilets at school, to comply with timed voiding which is part of the treatment for DV. This study investigated children's access to primary school toilets in Auckland. METHODS: A questionnaire was sent to 97 primary schools listed on the New Zealand ministry of education (MoE) website for the Auckland region. Information regarding the school decile rating, population, rota, toilet facilities and toilet policy was requested. Six randomly selected schools were visited to verify the facilities available there. RESULTS: Eighty-four percent of the schools in our sample complied with the prescribed statutory minimum for both boys and girls toilets. There was a median ratio of 11 children per facility. The median duration to use a facility during the first recess was 2 min. CONCLUSION: In general, the toilet facilities and utilization ratios in primary schools in the Auckland region appear to provide a healthy environment for urination. Schools must be encouraged to draft and adhere to a toilet policy to ensure a uniform toilet environment.