Kif9 is an active kinesin motor required for ciliary beating and proximodistal patterning of motile axonemes.

Most motile cilia have a stereotyped structure of nine microtubule outer doublets and a single central pair of microtubules. The central pair of microtubules are surrounded by a set of proteins, termed the central pair apparatus. A specific kinesin, Klp1 projects from the central pair and contributes to ciliary motility in Chlamydomonas. The vertebrate ortholog, Kif9, is required for beating in mouse sperm flagella, but the mechanism of Kif9/Klp1 function remains poorly defined. Here, using Xenopus epidermal multiciliated cells, we show that Kif9 is necessary for ciliary motility and the proper distal localization of not only central pair proteins, but also radial spokes and dynein arms. In addition, single-molecule assays in vitro reveal that Xenopus Kif9 is a long-range processive motor, although it does not mediate long-range movement in ciliary axonemes in vivo. Together, our data suggest that Kif9 is integral for ciliary beating and is necessary for proper axonemal distal end integrity.

Perceptions of government knowledge and control over contributions of aid organizations and INGOs to health in Nepal: a qualitative study.

BACKGROUND: Almost 50% of the Nepali health budget is made up of international aid. International Non-Governmental Organizations working in the field of health are able to channel their funds directly to grass root level. During a 2010 conference, the Secretary of Population stated that the government has full knowledge and control over all funds and projects coming to Nepal. However, there are no documents to support this. The study aims to assess government and partner perceptions on whether Government of Nepal currently has full knowledge of contributions of international aid organizations and International Non-Governmental Organizations to health in Nepal and to assess if the government is able to control all foreign contributions to fit the objectives of Second Long Term Health Plan (1997-2017). METHODS: A qualitative study was performed along with available literature review. Judgmental and snowball sampling led to 26 in depth interviews with key informants from the government, External Development Partners and International Non-Governmental Organizations. Results were triangulated based on source of data. Representatives of the Department of Health Services declined to be interviewed. Data collection was done until researchers felt data saturation had been reached with each group of key informants. RESULTS: While Ministry of Health and Population leads the sector wide approach that aims to integrate all donor and International Non-Governmental Organization contributions to health and direct them to the government's priority areas, questions were raised around its capacity to do so. Similarly, informants questioned the extent to which Social Welfare Council was able to control all International Non-Governmental Organizations contributions. Political tumult, corruption in the government, lack of human resources in the government, lack of coordination between government bodies, convoluted bureaucracy, and unreliability of donor and International Non-Governmental Organization contributions were identified as the main reasons for difficulties in aid integration. CONCLUSIONS: Despite its commitment to coordinate and control development assistance to the health sector, and its leadership position of the Sector Wide Approach, complete knowledge and effective coordination of all international contributions remains a challenge and is hampered by issues within the government as well as among External Development Partners and International Non-Governmental Organizations.

Landscape predictors influencing livestock depredation by leopards in and around Annapurna Conservation Area, Nepal.

Livestock depredation by leopards is a pervasive issue across many Asian and African range countries, particularly in and around protected areas. Developing effective conflict mitigation strategies requires understanding the landscape features influencing livestock depredation. In this study, we investigated predictors associated with livestock depredation by leopards using 274 cases of leopard attacks on livestock that occurred between 2017 and 2020 in the Annapurna Conservation Area, Nepal. We also examined how livestock predation by leopards varied depending on the species, season, and time. A generalized linear model with binary logistic regression was used to test the statistical significance of variables associated with the presence and absence of conflict sites. The results revealed that the area of forest, agricultural land, length of rivers, slope, proximity to settlements and protected areas, and elevation significantly predicted the probability of leopard attacks on livestock. We also observed a significant increase in the incidence of leopard predation on livestock with decreasing slopes and rising elevations. The areas near human settlements and the protected areas faced a higher risk of leopard predation. The incidence of leopard predation on livestock varied significantly depending on the livestock species, season, and time. Goats were the most highly predated livestock, followed by sheep, cow/ox, and buffalo. A total of 289.11 km2 (or around 5% of the research area) was deemed to be at high risk for leopard predation on livestock. This study's comprehensive understanding of human-leopard conflicts provides valuable insights for planning and implementing measures to reduce damage caused by leopard populations throughout their range.

Comparison of Functional and Radiological Outcomes of Transverse Patellar Fractures Fixed with Tension Band Fixation Using Cannulated Screws and Kirschner Wires: A Prospective Randomized Study.

PURPOSE: To compare functional and radiological outcomes of transverse patella fractures treated with tension band wiring using either two 4.5 mm cannulated screws or Kirshner wire. METHODS: This is a non-blinded prospective randomized study comprising of two groups (n = 30 each) with closed transverse patella fractures treated with tension band wiring using Kirschner wire (K wire group) and two 4.5 mm cannulated screws (CCS group). Outcomes measured were radiological union, Knee Society score, range of motion and post-operative complications. RESULTS: The CCS group showed a statistically significant higher range of motion than K wire group for each follow up (p < 0.001 in flexion and p < 0.005 in extension). A statistically significant higher percentage of patients in the CCS group showed signs of union at 6th and 12th post-operative week (p = 0.001 and 0.011 respectively) but no difference at 24th post-operative week (p = 0.313). The rate of hardware complications was significantly higher in K wire group (p = 0.001). No significant difference was noted in in the Knee society score and post-operative complications between the groups. CONCLUSION: This study concludes that the fixation of closed transverse patella fractures using two 4.5 mm cannulated screws is allows a faster rate of union, a better knee range of motion and lesser hardware complications as compared to Kirschner wires. However more studies with larger sample sizes and longer follow up are required.

Functional outcome of patients of tibial fracture treated with solid nail (SIGN nail) versus conventional hollow nail - A randomized trial.

BACKGROUND: Trauma related disabilities disproportionately affects low and middle income countries due to lack of resources, skills and optimal implants. Despite adequate animal studies, biomechanical studies, cohort studies and comparison studies we are not aware of any randomized trial to compare the functional outcome of SIGN (Surgical Implant Generation Network, US) solid nailing with a hollow nailing for tibial shaft fracture. METHODS: Sixty patients (≥16 years) of closed and Gustilo grade I traumatic fractures of the leg were randomized into SIGN solid nailing or hollow nailing group. Cases with compromised soft tissue and grossly deformed medullary canal were excluded. Functional outcome and need for resurgery were the primary outcomes while the secondary outcomes were duration of surgery, intraoperative blood loss, overall pain (VAS), radiological union (RUST), surgery related complications (infection, malalignment, shortening, nonunion) and pain/range of motion (ROM) of knee/ankle. All SIGN surgery related data were entered and retrieved online from www.signsurgery.org. RESULT: The demographical parameters were symmetrically distributed between the groups (p > 0.05). 2 cases in SIGN nailing and 4 cases in hollow nailing needed open reduction. The functional outcome, as assessed by blinded physiotherapist using Johner and Wruh criteria, was excellent in 18 (62.06%), good in 6 (20.68%), fair in 3 (10.34%) and poor in 2 (6.89%) for SIGN nail whereas it was 16 (57.14%), 8 (28.57%), 3 (10.71%) and 1 (3.57%) respectively for hollow nail. There was 1 case of implant failure and 1 case of infection. Intraoperative blood loss (397 ± 94.47 ml versus 350 ± 75.43 ml, p = 0.037) and duration of surgery (94.8 ± 14.57 min versus 82.0 ± 12.36 min, p = 0.001) were significantly more in hollow nailing group. At final follow up, overall pain on weight bearing (VAS score) and radiological union (RUST score) were 2.1 and 11.7 for SIGN nailing while they were 2.7 and 11.3 respectively for hollow nailing.(p = 0.41 and 0.45 respectively) The malrotation (p = 1.000), shortening (p = 1.000), varus-valgus angulation (p = 0.511), AP angulation (p = 0.706), ROM ankle (p = 0.239) and ROM knee (p = 0.086) were similar. CONCLUSION: Solid SIGN nailing gives comparable functional outcome as conventional hollow nailing for tibia shaft fracture. For developing world with limited resources, SIGN nail is useful which is supplied freely and is designed to be used without image intensifier and fracture table.

Suitability of Habitats in Nepal for Dactylorhiza hatagirea Now and under Predicted Future Changes in Climate.

Dactylorhiza hatagirea is a terrestrial orchid listed in Appendix II of the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) and classified as threatened by International Union for Conservation of Nature (IUCN). It is endemic to the Hindu-Kush Himalayan region, distributed from Pakistan to China. The main threat to its existence is climate change and the associated change in the distribution of its suitable habitats to higher altitudes due to increasing temperature. It is therefore necessary to determine the habitats that are suitable for its survival and their expected distribution after the predicted changes in climate. To do this, we use Maxent modelling of the data for its 208 locations. We predict its distribution in 2050 and 2070 using four climate change models and two greenhouse gas concentration trajectories. This revealed severe losses of suitable habitat in Nepal, in which, under the worst scenario, there will be a 71-81% reduction the number of suitable locations for D. hatagirea by 2050 and 95-98% by 2070. Under the most favorable scenario, this reduction will be 65-85% by 2070. The intermediate greenhouse gas concentration trajectory surprisingly would result in a greater reduction by 2070 than the worst-case scenario. Our results provide important guidelines that local authorities interested in conserving this species could use to select areas that need to be protected now and in the future.

Implications of landscape genetics and connectivity of snow leopard in the Nepalese Himalayas for its conservation.

The snow leopard is one of the most endangered large mammals. Its population, already low, is declining, most likely due to the consequences of human activity, including a reduction in the size and number of suitable habitats. With climate change, habitat loss may escalate, because of an upward shift in the tree line and concomitant loss of the alpine zone, where the snow leopard lives. Migration between suitable areas, therefore, is important because a decline in abundance in these areas may result in inbreeding, fragmentation of populations, reduction in genetic variation due to habitat fragmentation, loss of connectivity, bottlenecks or genetic drift. Here we use our data collected in Nepal to determine the areas suitable for snow leopards, by using habitat suitability maps, and describe the genetic structure of the snow leopard within and between these areas. We also determine the influence of landscape features on the genetic structure of its populations and reveal corridors connecting suitable areas. We conclude that it is necessary to protect these natural corridors to maintain the possibility of snow leopards' migration between suitable areas, which will enable gene flow between the diminishing populations and thus maintain a viable metapopulation of snow leopards.

Management of trochanteric fractures of the femur with external fixation in high-risk patients.

The aim of this prospective study was to assess the outcome of trochanteric fractures of the femur after external fixation in a group of elderly patients with high surgical risk. The study population consisted of 50 patients with trochanteric fractures of the femur and a mean age of 87 years who were classified by an anaesthetist as ASA 3 or 4 and considered not suitable for conventional fractures fixation. The fracture was fixed with an external fixator under spinal anaesthesia. The final follow-up was at 12 months. All fractures healed within 12 weeks. Superficial pin tract infection occurred in 30 patients, and fracture united with a shortening of 14 mm (5-20) in 12 patients. No implant failures or limitation of knee movements were recorded. Five patients died within 1 year. External fixation is a valuable treatment alternative for trochanteric fracture of the femur in elderly patients.

Diet and prey selection by snow leopards in the Nepalese Himalayas.

Visual attractiveness and rarity often results in large carnivores being adopted as flagship species for stimulating conservation awareness. Their hunting behaviour and prey selection can affect the population dynamics of their prey, which in turn affects the population dynamics of these large carnivores. Therefore, our understanding of their trophic ecology and foraging strategies is important for predicting their population dynamics and consequently for developing effective conservation programs. Here we concentrate on an endangered species of carnivores, the snow leopard, in the Himalayas. Most previous studies on snow leopard diet lack information on prey availability and/or did not genetically check, whether the identification of snow leopard scats is correct, as their scats are similar to those of other carnivores. We studied the prey of snow leopard in three Himalayan regions in Nepal (Sagarmatha National Park (SNP), Lower Mustang (LM) and Upper Manang (UM) in the Annapurna Conservation Area, during winter and summer in 2014-2016. We collected 268 scats along 139.3 km linear transects, of which 122 were genetically confirmed to belong to snow leopard. Their diet was identified by comparing hairs in scats with our reference collection of the hairs of potential prey. We determined prey availability using 32-48 camera-traps and 4,567 trap nights. In the SNP, the most frequent prey in snow leopard faeces was the Himalayan tahr in both winter and summer. In LM and UM, its main prey was blue sheep in winter, but yak and goat in summer. In terms of relative biomass consumed, yak was the main prey everywhere in both seasons. Snow leopard preferred large prey and avoided small prey in summer but not in winter, with regional differences. It preferred domestic to wild prey only in winter, and in SNP. Unlike most other studies carried out in the same area, our study uses genetic methods for identifying the source of the scat. Studies solely based on visual identification of samples may be strongly biased. Diet studies based on frequency of occurrence of prey tend to overestimate the importance of small prey, which may be consumed more often, but contribute less energy than large prey. However, even assessments based on prey biomass are unlikely to be accurate as we do not know whether the actual size of the prey consumed corresponds to the average size used to calculate the biomass eaten. For example, large adults may be too difficult to catch and therefore mostly young animals are consumed, whose weight is much lower. We show that snow leopard consumes a diverse range of prey, which varies both regionally and seasonally. We conclude that in order to conserve snow leopards it is also necessary to conserve its main wild species of prey, which will reduce the incidence of losses of livestock.

Long-term survival benefit of upfront chemotherapy in patients with newly diagnosed borderline resectable pancreatic cancer.

The use of neoadjuvant chemotherapy or radiation for borderline resectable pancreatic adenocarcinoma (BL-PDAC) is increasing. However, the impact of neoadjuvant chemotherapy and radiation therapy on the outcome of BL-PDAC remains to be elucidated. We performed a retrospective analysis of 93 consecutive patients who were diagnosed with BL-PDAC and primarily followed at Johns Hopkins Hospital between February 2007 and December 2012. Among 93 patients, 62% received upfront neoadjuvant chemotherapy followed by chemoradiation, whereas 20% received neoadjuvant chemoradiation alone and 15% neoadjuvant chemotherapy alone. Resectability following all neoadjuvant therapy was 44%. Patients who underwent resection with a curative intent had a median overall survival (mOS) of 25.8 months, whereas those who did not undergo surgery had a mOS of 11.9 months. However, resectability and overall survival were not significantly different between the three types of neoadjuvant therapy. Nevertheless, 22% (95% CI, 0.13-0.36) of the 58 patients who received upfront chemotherapy followed by chemoradiation remained alive for a minimum of 48 months compared to none of the 19 patients who received upfront chemoradiation. Among patients who underwent curative surgical resection, 32% (95% CI, 0.19-0.55) of those who received upfront chemotherapy remained disease free at least 48 months following surgical resection, whereas none of the eight patients who received upfront chemoradiation remained disease free beyond 24 months following surgical resection. Neoadjuvant therapy with upfront chemotherapy may result in long-term survival in a subpopulation of patients with BL-PDAC.

An unusual presentation of gastric mucosa-associated lymphoid tissue (MALT)-type lymphoma.

MALT: Mucosa-associated lymphoid tissue (MALT)-type lymphoma is a relatively rare disease; nevertheless, it is the third most common lymphoma type, accounting for 5-7% of all non-Hodgkin lymphomas. Case series and retrospective analysis published in the literature have suggested that extra gastrointestinal (GI) MALT-type lymphoma can occur simultaneously with MALT-type lymphoma involving the GI tract. We report the case of a healthy, 64-year-old Caucasian male who presented with progressive fatigue, non-productive cough, and worsening exertional shortness of breath for 3 months who was subsequently diagnosed with gastric extra-nodal marginal zone B-cell lymphoma or MALToma with simultaneous metastasis to the lung (bronchi) based on biopsy reports. CASE PRESENTATION: A 64-year-old Caucasian male presented to the emergency room complaining of progressive fatigue for 3 months which had progressed to the point of hindering his usual activities of daily living (ADL). He had recently visited his primary care provider for evaluation of a non-productive cough and exertional shortness of breath. A chest radiography obtained at the time showed bilateral infiltrates. He was then treated for atypical pneumonia but his symptoms unfortunately did not improve. Initial investigations in the emergency room revealed severe anemia and a positive stool guaiac test. Imaging showed bilateral pulmonary infiltrates and an irregular gastric mass. Gastric and transbronchial biopsies were suggestive of extra-nodal marginal zone B-cell lymphoma with simultaneous metastasis to the bronchi. He was treated symptomatically with transfusion of packed red blood cells (PRBC) and intravenous iron followed by radiotherapy. Helicobacter pylori infection was ruled out eliminating the possibility of treating him with eradication therapy. CONCLUSION: Although the stomach is the most common and most extensively studied site of involvement of MALT lymphomas, they can also emerge in many other locations. MALT lymphomas have a high tendency to disseminate to other sites; therefore, extensive staging may be necessary to look for suspicious lesions.

Comparison of Ponseti and Kite's method of treatment for idiopathic clubfoot.

BACKGROUND: The manipulation and corrective cast application for club foot was known to be done by Kite's method. The Kite's method of manipulation (center of rotation of malaligned foot and fulcrum on cuboid) was modified by Ponseti (fulcrum on head of talus). Recently, Ponseti's method has gained popularity and vastly improved results are reported. We report randomized controlled trial where manipulation of club foot was done by Ponseti's and Kite's method and correction evaluated by Pirani score to compare the outcome of treatment. MATERIALS AND METHODS: Sixty feet in 38 patients, 22 with bilateral and 16 with unilateral clubfeet in children less than two years of age and without any prior manipulation or surgical treatment were randomly allocated to the Ponseti (30 feet) and Kite (30 feet) methods of manipulation. This process resulted in the right and left feet of the same patient in 12 bilateral cases being compared with one another (Paired analysis). In the remaining 10 bilateral cases, four patients had both feet treated by Ponseti and six had both feet treated by Kite (unpaired analysis). Finally, in 16 unilateral cases, 10 feet were allocated to the Ponseti and six to Kite methods of manipulation (unpaired analysis). Feet were followed up weekly for 10 weeks for change of cast and recording of hindfoot, midfoot and total Pirani scores. Correction was measured as a difference between hindfoot, mid foot and total Pirani scores weekly from weeks 1 to 10 and corresponding baseline scores. Absolute correction and rate of correction in (i) bilateral clubfeet treated by Ponseti's method on one side and Kite's method on the other side in the same patient were compared using paired Student's t test and (ii) patients with unilateral clubfoot (where either of the methods was used) or those with bilateral clubfoot (where both feet treated by either of the two methods on both the sides) were compared using difference between means (mean correction by Ponseti minus mean correction by Kite) for magnitude of difference and unpaired Student's t test (if data was normally distributed) or Mann Whitney U statistics (otherwise) for significance of difference. RESULTS: In 12 bilateral clubfeet, where one foot received Kite's method and the other Ponseti's manipulation, feet treated by Ponseti's technique showed faster rates of decrease in Pirani score (improvement) as compared to feet treated by Kite's method with the mean of difference between baseline and follow up scores showing significantly greater (P<0.05) difference from zero from fourth week onwards to up to 10 weeks. In unpaired analysis, both for unilateral or bilateral clubfeet, regardless of side, mean Pirani scores in Ponseti feet improved much faster than Kite feet but the difference achieved statistical significance only at the 10(th) week from the start of treatment. CONCLUSIONS: Hind foot, midfoot and total Pirani scores reduce much faster with Ponseti than the Kite's method of manipulation of clubfoot. In paired analysis the difference becomes statistically significant at fourth week and in unpaired analysis at 10(th) week from the start of treatment.

Clinico-epidemiological study of spinal injuries in a predominantly rural population of eastern Nepal: A 10 years' analysis.

BACKGROUND: A clinico-epidemiological study helps to plan future preventive measures and management strategies for spinal trauma. This is a 10 years' retrospective review of spinal-injury patients treated at a tertiary health center in the eastern of Nepal to determine clinico-epidemiological aspects of spinal-injury patients in a predominantly rural population of eastern Nepal. MATERIALS AND METHODS: All medical record files of patients with spinal injury from 1996 to 2005 in the Medical Record Section of BPKIHS (B. P. Koirala Institute of Health Sciences) were studied. The preformed pro forma consisting age, sex, place of living, mode of injury, hospital stay level of injury, site of injury, associated injury, Frankel grading of neural deficit and treatment modality was filled from the record files of patients. These parameters were entered in Excel 8 and analyzed by EPI INFO 2002. Details of 896 patients of spinal injury were recorded in the 10-year period of review. RESULTS: 684 (76.35%) male and 212 (23.66%) female patients with mean age of 41.74 ± 16.53 years and 38.56 ± 15.86 years respectively were studied. Two hundred forty-two (27%) patients were from hilly districts of eastern Nepal. Fall from height [in 350 (39%) patients] was the commonest mode of spinal injury. Six hundred thirty-six (71%) patients presented with a neurological deficit. Seven hundred thirty-three (85%) patients were treated conservatively, compared to 163 (15%) surgically treated patients. One hundred forty-six (22%) patients were treated with operative interventions in the last five years. CONCLUSION: The study shows that the most vulnerable group for spine injury was the group of patients of productive age with late presentation (i.e., injury hospital duration - 41.64 ± 54.24 hours) without proper prehospital management. The treatment modalities have changed (from conservative to surgical) in this part of the world. These specific observations help us in further planning for preventive measures and management in our setting.

Tumor de células gigantes da extremidade distal do fêmur: um desafio de tratamento / Giant cell tumor of femoral distal end: a challenge in treatment

Apresentamos aqui um caso de tumor de células gigantes na extremidade distal do fêmur direito tratado com ressecção da massa tumoral em bloco com remoção aguda da extremidade proximal e distal e fixado com hastes longas em K atravessando o joelho, do fêmur à tíbia. Após a consolidação / união completa das extremidades, foi feita a remoção da haste em K, seguida pela corticotomia juntamente com a osteogênese da distração com o auxílio do anel fixador de Ilizarov. O comprimento foi alcançado com este processo. O resultado final foi muito bom neste caso. Revisamos as opções de tratamento para tumor maligno de células gigantes na extremidade distal do fêmur e as dificuldades de tratá-lo.

We present a case of malignant giant cell tumor of distal end of right femur treated with resection of the tumor mass en block with acute docking of proximal and distal end and fixed with long K-nail across knee from femur to tibia. After complete consolidation/ union of the ends, removal of K nail was done followed by corticotomy along with distraction osteogenesis with the help of Ilizarov ring fixator. The length was achieved with this process. The end result was very good in this case. We reviewed the treatment options for malignant giant cell tumor of femoral distal end and the challenges in its treatment.