Managing memory deficits is a central problem among older adults with mild cognitive impairment (MCI). This study examined the effects of memory training on memory performance in an understudied “oldest-old” populat...Managing memory deficits is a central problem among older adults with mild cognitive impairment (MCI). This study examined the effects of memory training on memory performance in an understudied “oldest-old” population ranging in age from 90 to 99 years. Eighteen mild to moderately cognitive-impaired older seniors, 90 years and older were recruited from memory clinics established in senior living communities. Treatment sessions took place, on average, twice weekly, for 55 minutes. Memory intervention included nineteen computer-based exercises customized to focus on memory loss. The specificity of memory training was very clear;memory training produced significant effects (F(3,51) = 2.81, p = 0.05) on memory performance, especially after 6 months of training, while other outcome measures showed no effects as predicted. Based on the results, it can be concluded that interventions targeting cognition and memory in the oldest-old MCI population can significantly improve memory function and reduce cognitive deficits.展开更多
Background: The nutritional support after hematopoietic stem cell transplantation (HSCT) has not been well established due to the scarcity of clinical trials. To conduct international clinical trials in Asia, we perfo...Background: The nutritional support after hematopoietic stem cell transplantation (HSCT) has not been well established due to the scarcity of clinical trials. To conduct international clinical trials in Asia, we performed the questionnaire survey to investigate the current standard of nutritional support after HSCT. Method: We sent the questionnaire to the physicians nominated by the Asia Pacific Blood and Marrow Transplantation (APBMT) members of each country/ region. Result: We received 15 responses from 7 different countries/regions. The target calorie amount is 1.0 - 1.3 × basal energy expenditure (BEE) in 11 institutes when partial parenteral nutrition is used. When total parenteral nutrition (TPN) is used, the target calorie amount is 1.0 - 1.3 × BEE in 9 institutes and 1.3 - 1.5 × BEE in 4 institutes. Lipid emulsion is routinely used in 12 institutes. Multivitamins and trace elements are routinely added to TPN used in most institutes. It is still uncommon to use the immunonutrition. Blood glucose levels are routinely monitored in all institutes, but the target range varies (<110 in 2 institutes, <150 in 4 institutes, and <200 in 8 institutes). Conclusions: Basic nutritional support is similar in participating institutes. However, the target glucose level varies and the use of immunonutrition is rather rare. These points can be the theme of future clinical trials.展开更多
The effects of a memory training paradigm on performance across multiple cognitive domains, measured via the Cognistat, in 70 - 89 year-old individuals with mild cognitive impairment (MCI), were examined. Memory train...The effects of a memory training paradigm on performance across multiple cognitive domains, measured via the Cognistat, in 70 - 89 year-old individuals with mild cognitive impairment (MCI), were examined. Memory training sessions were conducted on average twice weekly, for 55 minutes each session, for 9 months. Across the testing period, Cognistat-measured memory increased relative to performance in other cognitive domains. Additionally, performance on non-memory measures remained stable or declined. Thus, memory training in older adult, MCI individuals may result in improved memory, but not in improvement in other, non-memory, cognitive domains. Results replicate previous work examining “oldest-old” individuals ranging in age from 90 to 99 years old at the time of study start.展开更多
Subjective memory impairment is a major complaint among older adults;however, research is conflicting regarding the relationship between subjective memory impairment and objectively measured memory loss. Here, individ...Subjective memory impairment is a major complaint among older adults;however, research is conflicting regarding the relationship between subjective memory impairment and objectively measured memory loss. Here, individuals with mild memory impairment completed the memory subscale of the Cognistat as a measure of objective memory, and the Memory Complaint Questionnaire (MCQ) as a measure of subjective memory, prior to and following a 3-month memory training program. Results revealed that individuals with more, compared with fewer, memory complaints performed worse on the Cognistat. Additionally, increased Cognistat performance fol-lowing the memory training procedure was associated with decreased MCQ measured complaints. There was suggestive evidence that the memory training procedure improved memory, and thus future research is warranted. These findings imply that older, memory-impaired, adults, despite their memory impairment, are indeed able to judge, and may be accurately concerned with, the extent of their own memory loss. It should be noted that serious statistical limitations here indicate the need for replication to confirm the validity of the findings.展开更多
BACKGROUND Pancreaticoduodenectomy(PD)is a technically complex operation,with a re-latively high risk for complications.The ability to rescue patients from post-PD complications is as a recognized quality measure.Tail...BACKGROUND Pancreaticoduodenectomy(PD)is a technically complex operation,with a re-latively high risk for complications.The ability to rescue patients from post-PD complications is as a recognized quality measure.Tailored protocols were instituted at our low volume facility in the year 2013.AIM To document the rate of rescue from post-PD complications with tailored protocols in place as a measure of quality.METHODS A retrospective audit was performed to collect data from patients who experienced major post-PD complications at a low volume pancreatic surgery unit in Trinidad and Tobago between January 1,2013 and June 30,2023.Stan-dardized definitions from the International Study Group of Pancreatic Surgery were used to define post-PD complications,and the modified Clavien-Dindo classification was used to classify post-PD complications.RESULTS Over the study period,113 patients at a mean age of 57.5 years(standard deviation[SD]±9.23;range:30-90;median:56)underwent PDs at this facility.Major complications were recorded in 33(29.2%)patients at a mean age of 53.8 years(SD:±7.9).Twenty-nine(87.9%)patients who experienced major morbidity were salvaged after aggre-ssive treatment of their complication.Four(3.5%)died from bleeding pseudoaneurysm(1),septic shock secondary to a bile leak(1),anastomotic leak(1),and myocardial infarction(1).There was a significantly greater salvage rate in patients with American Society of Anesthesiologists scores≤2(93.3%vs 25%;P=0.0024).CONCLUSION This paper adds to the growing body of evidence that volume alone should not be used as a marker of quality for patients requiring PD.Despite low volumes at our facility,we demonstrated that 87.9%of patients were rescued from major complications.We attributed this to several factors including development of rescue protocols,the competence of the pancreatic surgery teams and continuous,and adaptive learning by the entire institution,cul-minating in the development of tailored peri-pancreatectomy protocols.展开更多
Background of the Study: Femoral shaft fracture is the most common pediatric injury requiring hospitalization. For children less than 5 years old, non-surgical approach is recommended. For pediatric patients 5 - 14 ye...Background of the Study: Femoral shaft fracture is the most common pediatric injury requiring hospitalization. For children less than 5 years old, non-surgical approach is recommended. For pediatric patients 5 - 14 years old, the most common mode of treatment is flexible intramedullary nailing with a known complication of pain at post-op site, inflammatory reaction/bursitis at the entry site, superficial and deep infection, knee synovitis, knee stiffness, leg length discrepancy, proximal nail migration, angulation or malunion, delayed and non-union, implant breakage. This study aims to present a rare complication of a femoral fracture fixed with flexible intramedullary nail. Methodology: We report the outcome of a 12-year-old male with peri implant fracture of the left femur. He underwent removal of plates and screws and subsequently fixed with flexible intramedullary nails. Patient was followed up at 1, 3, 7, and 10 months post-operatively. Varus-valgus, sagittal angulation, and limb shortening were measured pre- and post-operatively. Complications were recorded on each visit. Results: Pre-operative varus angulation was 10˚, pro-curvatum of 55˚ with limb shortening of 4 cm. Postoperatively, varus was maintained to 10˚ but pro-curvatum was corrected to 4˚ and limb shortening was reduced to 1 cm. However, after 1 month the varus angulation increased to 30˚ while maintaining sagittal pro-curvatum. Limb shortening also increased to 2 cm. New bone formation started to appear along the mechanical axis of the left femur which is apparent at 3 months post-op and pro-curvatum increased to 20˚. At 7 and 10 months post-op no signs of union was noted at the fracture site but the callus formation along the mechanical axis gradually matured and appeared as a new femoral shaft. Conclusion: Formation of new bone in response to unstable flexible intramedullary fixation in pediatric femoral shaft fracture is a very rare complication.展开更多
Cyclops lesion is a fibrous nodule on the tibial side of the knee and it is one of the common complications that arises after anterior cruciate ligament (ACL) reconstruction, causing loss of knee extension. A presenta...Cyclops lesion is a fibrous nodule on the tibial side of the knee and it is one of the common complications that arises after anterior cruciate ligament (ACL) reconstruction, causing loss of knee extension. A presentation dominated by recurrent hemarthrosis is a rare presentation of this lesion. In this case report, we have discussed about a male patient who presented with recurrent hemarthrosis and inability to extend the knee joint fully 8 months after ACL reconstruction. Cyclops lesion was identified by clinical examination and magnetic resonance imaging (MRI). Recurrence after initial excision of the lesion occurred and complete resolution happened during the second operation when cauterization was done. It is imperative that treatment should include coagulation of the vascularized stump to avoid any recurrence.展开更多
Astrocytes are associated with varying brain size between rodents and primates.As a close evolutionary relative of primates,the tree shrew(Tupaia belangeri)provides a valuable comparative model for investigating glial...Astrocytes are associated with varying brain size between rodents and primates.As a close evolutionary relative of primates,the tree shrew(Tupaia belangeri)provides a valuable comparative model for investigating glial architecture.However,the anatomical distribution and morphological characteristics of astrocytes in the tree shrew brain remain poorly characterized.In this study,glial fibrillary acidic protein(GFAP)immunofluorescence was employed to systematically examine the spatial distribution and morphology of astrocytes in the whole brain of tree shrews.Notably,GFAP-immunoreactive(ir)astrocytes were detected throughout the telencephalon,diencephalon,mesencephalon,metencephalon,and myelencephalon.Distinct laminar distribution was evident in regions such as the main olfactory bulb and hippocampus.Semi-quantitative comparisons revealed significant regional differences in astrocyte density between tree shrews and mice,encompassing the main olfactory bulb,accessory olfactory bulb,olfactory tubercle,cortex,hippocampus,cortical amygdaloid nucleus,hypothalamus,thalamus,superior colliculus,interpeduncular nucleus,median raphe nucleus,and parabrachial nucleus.Compared to mice,tree shrews exhibited higher astrocyte density with increased morphological complexity in the posterior hypothalamic nucleus,dorsomedial hypothalamic nucleus,ventromedial hypothalamic nucleus,and periaqueductal gray,but lower density with greater morphological complexity in the hippocampus and substantia nigra.In the paraventricular hypothalamic nucleus and lateral hypothalamic area,GFAP-ir astrocytes displayed comparable densities between tree shrews and mice but exhibited region-specific differences in morphological complexity.This study provides the first brain-wide mapping of GFAP-ir astrocytes in tree shrews,revealing marked interspecies differences in their distribution and morphology,and establishing a neuroanatomical framework for understanding astrocyte involvement in diverse physiological and behavioral functions.展开更多
Over the past three decades,there has been increasing interest in miniaturized percutaneous nephrolithotomy(mPCNL)techniques featuring smaller tracts as they offer potential solutions to mitigate complications associa...Over the past three decades,there has been increasing interest in miniaturized percutaneous nephrolithotomy(mPCNL)techniques featuring smaller tracts as they offer potential solutions to mitigate complications associated with standard PCNL(sPCNL).However,despite this growing acceptance and recognition of its benefits,unresolved controversies and acknowledged limitations continue to impede widespread adoption due to a lack of consensus on optimal perioperative management strategies and procedural tips and tricks.In response to these challenges,an international panel comprising experts from the International Alliance of Urolithiasis(IAU)took on the task of compiling an expert consensus document on mPCNL procedures aimed at providing urologists with a comprehensive clinical framework for practice.This endeavor involved conducting a systematic literature review to identify research gaps(RGs),which formed the foundation for developing a structured questionnaire survey.Subsequently,a two-round modified Delphi survey was implemented,culminating in a group meeting to generate final evidence-based comments.All 64 experts completed the second-round survey,resulting in a response rate of 100.0%.Fifty-eight key questions were raised focusing on mPCNLs within 4 main domains,including general information(13 questions),preoperative work-up(13 questions),procedural tips and tricks(19 questions),and postoperative evaluation and follow-up(13 questions).Additionally,9 questions evaluated the experts’experience with PCNLs.Consensus was reached on 30 questions after the second-round survey,while professional statements for the remaining 28 key questions were provided after discussion in an online panel meeting.mPCNL,characterized by a tract smaller than 18 Fr and an innovative lithotripsy technique,has firmly established itself as a viable and effective approach for managing upper urinary tract stones in both adults and pediatrics.It offers several advantages over sPCNL including reduced bleeding,fewer requirements for nephrostomy tubes,decreased pain,and shorter hospital stays.The series of detailed techniques presented here serve as a comprehensive guide for urologists,aiming to improve their procedural understanding and optimize patient outcomes.展开更多
Cyclin-dependent kinase 1 （Cdkl）/cyclin B1 complex is the driving force for mitotic entry, and its activation is tightly regulated by the G2/M checkpoint. We originally reported that a novel protein C53 （also known...Cyclin-dependent kinase 1 （Cdkl）/cyclin B1 complex is the driving force for mitotic entry, and its activation is tightly regulated by the G2/M checkpoint. We originally reported that a novel protein C53 （also known as Cdk5rap3 and LZAP） potentiates DNA damage-induced cell death by modulating the G2/M checkpoint. More recently, Wang et al. （2007） found that C53/LZAP may function as a tumor suppressor by way of inhibiting NF-kB signaling. We re- port here the identification of C53 protein as a novel regulator of Cdkl activation. We found that knockdown of C53 protein causes delayed Cdkl activation and mitotic entry. During DNA damage response, activation of checkpoint kinase 1 and 2 （Chkl and Chk2） is partially inhibited by C53 overexpression. Intriguingly, we found that C53 inter- acts with Chkl and antagonizes its function. Moreover, a portion of C53 protein is localized at the centrosome, and centrosome-targeting C53 potently promotes local Cdkl activation. Taken together, our results strongly suggest that C53 is a novel negative regulator of checkpoint response. By counteracting Chkl, C53 promotes Cdkl activation and mitotic entry in both unperturbed cell-cycle progression and DNA damage response.展开更多
The diagnosis and management of obscure gastrointestinal bleeding(OGIB) have changed dramatically since the introduction of video capsule endoscopy(VCE) followed by deep enteroscopy and other imaging technologies in t...The diagnosis and management of obscure gastrointestinal bleeding(OGIB) have changed dramatically since the introduction of video capsule endoscopy(VCE) followed by deep enteroscopy and other imaging technologies in the last decade. Significant advances have been made, yet there remains room for improvement in our diagnostic yield and treatment capabilities for recurrent OGIB. In this review, we will summarize the latest technologies for the diagnosis of OGIB, limitations of VCE, technological enhancement in VCE, and different management options for OGIB.展开更多
Anal cancer represents less than 1% of all new cancers diagnosed annually in the United States. Yet, despite the relative paucity of cases, the incidence of anal cancer has seen a steady about 2% rise each year over t...Anal cancer represents less than 1% of all new cancers diagnosed annually in the United States. Yet, despite the relative paucity of cases, the incidence of anal cancer has seen a steady about 2% rise each year over the last decade. As such, all healthcare providers need to be cognizant of the evaluation and treatment of anal squamous cell carcinoma. While chemoradiation remains the mainstay of therapy for most patients with anal cancer, surgery may still be required in recurrent, recalcitrant and palliative disease. In this manuscript, we will explore the diagnosis and management of squamous cell carcinoma of the anus.展开更多
Despite multiple efforts aimed at early detection through screening, colon cancer remains the third leading cause of cancer-related deaths in the United States, with an estimated 51000 deaths during 2013 alone. The go...Despite multiple efforts aimed at early detection through screening, colon cancer remains the third leading cause of cancer-related deaths in the United States, with an estimated 51000 deaths during 2013 alone. The goal remains to identify and remove benign neoplastic polyps prior to becoming invasive cancers. Polypoid lesions of the colon vary widely from hyperplastic, hamartomatous and inflammatory to neoplastic adenomatous growths. Although these lesions are all benign, they are common, with up to one-quarter of patients over 60 years old will develop pre-malignant adenomatous polyps. Colonoscopy is the most effective screening tool to detect polyps and colon cancer, although several studies have demonstrated missed polyp rates from 6%-29%, largely due to variations in polyp size. This number can be as high as 40%, even with advanced (> 1 cm) adenomas. Other factors including sub-optimal bowel preparation, experience of the endoscopist, and patient anatomical variations all affect the detection rate. Additional challenges in decision-making exist when dealing with more advanced, and typically larger, polyps that have traditionally required formal resection. In this brief review, we will explore the recent advances in polyp detection and therapeutic options.展开更多
Progression of cells from G2 phase of the cell cycle to mitosis is a tightly regulated cellular process that requires activation of the Cdc2 kinase, which determines onset of mitosis in all eukaryotic cells. In both h...Progression of cells from G2 phase of the cell cycle to mitosis is a tightly regulated cellular process that requires activation of the Cdc2 kinase, which determines onset of mitosis in all eukaryotic cells. In both human and fission yeast (Schizosaccharomyces pombe) cells, the activity of Cdc2 is regulated in part by the phosphorylation status of tyrosine 15 (Tyr15) on Cdc2, which is phosphorylated by Wee1 kinase during late G2 and is rapidly dephosphorylated by the Cdc25 tyrosine phosphatase to trigger entry into mitosis. These Cdc2 regulators are the downstream targets of two well- characterized G2/M checkpoint pathways which prevent cells from entering mitosis when cellular DNA is damaged or when DNA replication is inhibited. Increasing evidence suggests that Cdc2 is also commonly targeted by viral proteins, which modulate host cell cycle machinery to benefit viral survival or replication. In this review, we describe the effect of viral protein R (Vpr) encoded by human immunodeficiency virus type 1 (HIV-1) on cell cycle G2/M regulation. Based on our current knowledge about this viral effect, we hypothesize that Vpr induces cell cycle G2 arrest through a mechanism that is to some extent different from the classic G2/M checkpoints. One the unique features distinguishing Vpr-induced G2 arrest from the classic checkpoints is the role of phosphatase 2A (PP2A) in Vpr-induced G2 arrest. Interestingly, PP2A is targeted by a number of other viral proteins including SV40 small T antigen, polyomavirus T antigen, HTLV Tax and adenovirus E4orf4. Thus an in-depth understanding of the molecular mechanisms underlying Vpr-induced G2 arrest will provide additional insights into the basic biology of cell cycle G2/M regulation and into the biological significance of this effect during host-pathogen interactions.展开更多
To investigate of pediatric ulcerative colitis activity index(PUCAI)in ulcerative colitis correlate with mucosal inflammation and endoscopic assessment of disease activity(Mayo endoscopic score).METHODSWe reviewed cha...To investigate of pediatric ulcerative colitis activity index(PUCAI)in ulcerative colitis correlate with mucosal inflammation and endoscopic assessment of disease activity(Mayo endoscopic score).METHODSWe reviewed charts from ulcerative colitis patients who had undergone both colonoscopy over 3 years.Clinical assessment of disease severity within 35 d(either before or after)the colonoscopy were included.Patients were excluded if they had significant therapeutic interventions(such as the start of corticosteroids or immunosuppressive agents)between the colonoscopy and the clinical assessment.Mayo endoscopic score of the rectum and sigmoid were done by two gastroenterologists.Inter-observer variability in Mayo score was assessed.RESULTSWe identified 99 patients(53%female,74%pancolitis)that met inclusion criteria.The indications for colonoscopy included ongoing disease activity(62%),consideration of medication change(10%),assessment of medication efficacy(14%),and cancer screening(14%).Based on PUCAI scores,33%of patients were in remission,39%had mild disease,23%had moderate disease,and 4%had severe disease.There was“moderate-substantial”agreement between the two reviewers in assessing rectal Mayo scores(kappa=0.54,95%CI:0.41-0.68).CONCLUSIONEndoscopic disease severity(Mayo score)assessed by reviewing photographs of pediatric colonoscopy has moderate inter-rater reliability,and agreement was less robust in assessing patients with mild disease activity.Endoscopic disease severity generally correlates with clinical disease severity as measured by PUCAI score.However,children with inflamed colons can have significant variation in their reported clinical symptoms.Thus,assessment of both clinical symptoms and endoscopic disease severity may be required in future clinical studies.展开更多
Prosthetic joint infections(PJIs),although not very common,currently pose a very significant threat since they are associated with severe complications,high morbidity rates and substantial costs.PJIs are most commonly...Prosthetic joint infections(PJIs),although not very common,currently pose a very significant threat since they are associated with severe complications,high morbidity rates and substantial costs.PJIs are most commonly caused by Staphylococcus aureus and coagulase-negative staphylococci.The diagnosis of implant-associated infections is very challenging since no single routinely used laboratory or clinical test has been shown to demonstrate adequate results with respect to sensitivity,specificity and accuracy.In most cases,a sum of clinical signs and symptoms,histopathology,blood tests,radiography,bone scans and microbiological testing is considered to arrive at an accurate diagnosis.Treatment of PJIs is also very difficult since most of the infections are caused by biofilm-producing microorganisms which are significantly more resistant to the hosts natural defense mechanisms and antibiotic treatment.For successful management,a combination of both antibiotic and surgical treatment is most often required,and early diagnosis is of the utmost importance.Thus,a multidisciplinary approach is potentially the best option in dealing with PJI,and should include the involvement of microbiologists,orthopedic specialists,clinicians,pathologists and radiologists in order to improve decision-making processes and ensure overall success.The following review aims at briefly outlining the microbiology,diagnostic and treatment options,and preventive measures associated with such infections.展开更多
BACKGROUND Alzheimer’s disease(AD)is among the most prevalent forms of dementia in the world and neuropathological studies suggest similar high prevalence of mixed(AD+vascular)dementias.Approximately 25%-50%of indivi...BACKGROUND Alzheimer’s disease(AD)is among the most prevalent forms of dementia in the world and neuropathological studies suggest similar high prevalence of mixed(AD+vascular)dementias.Approximately 25%-50%of individuals with AD develop psychosis sometime during their illness.The presence of psychosis in AD worsens outcomes.Currently there are no United States Food and Drug Administration(FDA)approved medications for the treatment of psychosis in AD.Pimavanserin,a novel atypical antipsychotic medication,was approved by the FDA for the treatment of hallucinations and delusions associated with Parkinson disease psychosis and is currently in clinical trials for the treatment of psychosis in AD.AIM To evaluate the existing literature regarding the use of pimavanserin for treating psychosis among individuals with AD.METHODS A literature review of clinical studies of pimavanserin treatment for psychosis in individuals with AD was performed using the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines.Trials were identified by systematically searching PubMed,MEDLINE,EMBASE,Cochrane Central Register of Controlled Trials,Web of Science,and Scopus through October 2019.The 5-point Jadad scoring system was used to assess the methodologic quality of the randomized placebo-controlled trials.RESULTS A total of 499 citations were retrieved and pooled in EndNote and de-duplicated to 258 citations.This set was uploaded to Covidence for screening.Two separate screeners(Srinivasan S and Tampi RR)evaluated the titles,abstracts,and full text of eligible articles.Of the identified 258 abstracts,98 articles underwent full text review and 2 publications from 1 randomized controlled trial(RCT)were included in the final analysis.The quality of evidence was assessed to be of good methodologic quality,scoring 4 out of 5 using the 5-point Jadad questionnaire with the Jadad Scoring calculation.This systematic review found only one RCT that evaluated the use of pimavanserin for the treatment of psychosis among individuals with AD.This phase 2 trial resulted in two publications,the second of which was a subgroup analysis from the original study.The evidence from these two publications showed that pimavanserin improves psychotic symptoms among individuals with AD when compared to placebo at week 6.CONCLUSION Pimavanserin may be a pharmacologic consideration for the treatment for psychosis in AD.Additional RCTs are needed to assess the evidence of effectiveness before pimavanserin is considered a standard treatment.展开更多
Hepatitis C is a strong prognostic factor for patients with hepatocellular carcinoma(HCC). Although liver resection and liver transplantation offer the chance of a cure for HCC,adequate management of co-existing infec...Hepatitis C is a strong prognostic factor for patients with hepatocellular carcinoma(HCC). Although liver resection and liver transplantation offer the chance of a cure for HCC,adequate management of co-existing infection with hepatitis C virus(HCV) is important to enable better long-term outcomes after surgery for HCV-related HCC. For patients undergoing liver resection,perioperative anti-viral treatment is recommended,since a decreased HCV viral load itself is reportedly associated with a lower tumor recurrence rate and a longer overall survival. For patients undergoing transplanatations for HCC complicated by end-stage liver disease,the post-transplant management of HCV infection is also necessary to prevent progressive graft injury caused by active hepatitis under the immunosuppressive condition that is needed after liver transplantation. Although only a few lines of solid evidence are available for postoperative antiviral treatment because of the limited indication and frequent adverse events caused by conventional high-dose combination interferon therapy,new direct acting anti-viral agents would enable interferon-free anti-viral treatment with a higher virologic response and minimal side effects.展开更多
文摘Managing memory deficits is a central problem among older adults with mild cognitive impairment (MCI). This study examined the effects of memory training on memory performance in an understudied “oldest-old” population ranging in age from 90 to 99 years. Eighteen mild to moderately cognitive-impaired older seniors, 90 years and older were recruited from memory clinics established in senior living communities. Treatment sessions took place, on average, twice weekly, for 55 minutes. Memory intervention included nineteen computer-based exercises customized to focus on memory loss. The specificity of memory training was very clear;memory training produced significant effects (F(3,51) = 2.81, p = 0.05) on memory performance, especially after 6 months of training, while other outcome measures showed no effects as predicted. Based on the results, it can be concluded that interventions targeting cognition and memory in the oldest-old MCI population can significantly improve memory function and reduce cognitive deficits.
文摘Background: The nutritional support after hematopoietic stem cell transplantation (HSCT) has not been well established due to the scarcity of clinical trials. To conduct international clinical trials in Asia, we performed the questionnaire survey to investigate the current standard of nutritional support after HSCT. Method: We sent the questionnaire to the physicians nominated by the Asia Pacific Blood and Marrow Transplantation (APBMT) members of each country/ region. Result: We received 15 responses from 7 different countries/regions. The target calorie amount is 1.0 - 1.3 × basal energy expenditure (BEE) in 11 institutes when partial parenteral nutrition is used. When total parenteral nutrition (TPN) is used, the target calorie amount is 1.0 - 1.3 × BEE in 9 institutes and 1.3 - 1.5 × BEE in 4 institutes. Lipid emulsion is routinely used in 12 institutes. Multivitamins and trace elements are routinely added to TPN used in most institutes. It is still uncommon to use the immunonutrition. Blood glucose levels are routinely monitored in all institutes, but the target range varies (<110 in 2 institutes, <150 in 4 institutes, and <200 in 8 institutes). Conclusions: Basic nutritional support is similar in participating institutes. However, the target glucose level varies and the use of immunonutrition is rather rare. These points can be the theme of future clinical trials.
文摘The effects of a memory training paradigm on performance across multiple cognitive domains, measured via the Cognistat, in 70 - 89 year-old individuals with mild cognitive impairment (MCI), were examined. Memory training sessions were conducted on average twice weekly, for 55 minutes each session, for 9 months. Across the testing period, Cognistat-measured memory increased relative to performance in other cognitive domains. Additionally, performance on non-memory measures remained stable or declined. Thus, memory training in older adult, MCI individuals may result in improved memory, but not in improvement in other, non-memory, cognitive domains. Results replicate previous work examining “oldest-old” individuals ranging in age from 90 to 99 years old at the time of study start.
文摘Subjective memory impairment is a major complaint among older adults;however, research is conflicting regarding the relationship between subjective memory impairment and objectively measured memory loss. Here, individuals with mild memory impairment completed the memory subscale of the Cognistat as a measure of objective memory, and the Memory Complaint Questionnaire (MCQ) as a measure of subjective memory, prior to and following a 3-month memory training program. Results revealed that individuals with more, compared with fewer, memory complaints performed worse on the Cognistat. Additionally, increased Cognistat performance fol-lowing the memory training procedure was associated with decreased MCQ measured complaints. There was suggestive evidence that the memory training procedure improved memory, and thus future research is warranted. These findings imply that older, memory-impaired, adults, despite their memory impairment, are indeed able to judge, and may be accurately concerned with, the extent of their own memory loss. It should be noted that serious statistical limitations here indicate the need for replication to confirm the validity of the findings.
基金This study was approved by the Campus Research Ethics Committee,St.Augustine.
文摘BACKGROUND Pancreaticoduodenectomy(PD)is a technically complex operation,with a re-latively high risk for complications.The ability to rescue patients from post-PD complications is as a recognized quality measure.Tailored protocols were instituted at our low volume facility in the year 2013.AIM To document the rate of rescue from post-PD complications with tailored protocols in place as a measure of quality.METHODS A retrospective audit was performed to collect data from patients who experienced major post-PD complications at a low volume pancreatic surgery unit in Trinidad and Tobago between January 1,2013 and June 30,2023.Stan-dardized definitions from the International Study Group of Pancreatic Surgery were used to define post-PD complications,and the modified Clavien-Dindo classification was used to classify post-PD complications.RESULTS Over the study period,113 patients at a mean age of 57.5 years(standard deviation[SD]±9.23;range:30-90;median:56)underwent PDs at this facility.Major complications were recorded in 33(29.2%)patients at a mean age of 53.8 years(SD:±7.9).Twenty-nine(87.9%)patients who experienced major morbidity were salvaged after aggre-ssive treatment of their complication.Four(3.5%)died from bleeding pseudoaneurysm(1),septic shock secondary to a bile leak(1),anastomotic leak(1),and myocardial infarction(1).There was a significantly greater salvage rate in patients with American Society of Anesthesiologists scores≤2(93.3%vs 25%;P=0.0024).CONCLUSION This paper adds to the growing body of evidence that volume alone should not be used as a marker of quality for patients requiring PD.Despite low volumes at our facility,we demonstrated that 87.9%of patients were rescued from major complications.We attributed this to several factors including development of rescue protocols,the competence of the pancreatic surgery teams and continuous,and adaptive learning by the entire institution,cul-minating in the development of tailored peri-pancreatectomy protocols.
文摘Background of the Study: Femoral shaft fracture is the most common pediatric injury requiring hospitalization. For children less than 5 years old, non-surgical approach is recommended. For pediatric patients 5 - 14 years old, the most common mode of treatment is flexible intramedullary nailing with a known complication of pain at post-op site, inflammatory reaction/bursitis at the entry site, superficial and deep infection, knee synovitis, knee stiffness, leg length discrepancy, proximal nail migration, angulation or malunion, delayed and non-union, implant breakage. This study aims to present a rare complication of a femoral fracture fixed with flexible intramedullary nail. Methodology: We report the outcome of a 12-year-old male with peri implant fracture of the left femur. He underwent removal of plates and screws and subsequently fixed with flexible intramedullary nails. Patient was followed up at 1, 3, 7, and 10 months post-operatively. Varus-valgus, sagittal angulation, and limb shortening were measured pre- and post-operatively. Complications were recorded on each visit. Results: Pre-operative varus angulation was 10˚, pro-curvatum of 55˚ with limb shortening of 4 cm. Postoperatively, varus was maintained to 10˚ but pro-curvatum was corrected to 4˚ and limb shortening was reduced to 1 cm. However, after 1 month the varus angulation increased to 30˚ while maintaining sagittal pro-curvatum. Limb shortening also increased to 2 cm. New bone formation started to appear along the mechanical axis of the left femur which is apparent at 3 months post-op and pro-curvatum increased to 20˚. At 7 and 10 months post-op no signs of union was noted at the fracture site but the callus formation along the mechanical axis gradually matured and appeared as a new femoral shaft. Conclusion: Formation of new bone in response to unstable flexible intramedullary fixation in pediatric femoral shaft fracture is a very rare complication.
文摘Cyclops lesion is a fibrous nodule on the tibial side of the knee and it is one of the common complications that arises after anterior cruciate ligament (ACL) reconstruction, causing loss of knee extension. A presentation dominated by recurrent hemarthrosis is a rare presentation of this lesion. In this case report, we have discussed about a male patient who presented with recurrent hemarthrosis and inability to extend the knee joint fully 8 months after ACL reconstruction. Cyclops lesion was identified by clinical examination and magnetic resonance imaging (MRI). Recurrence after initial excision of the lesion occurred and complete resolution happened during the second operation when cauterization was done. It is imperative that treatment should include coagulation of the vascularized stump to avoid any recurrence.
基金supported by the STI2030-Major Projects(2022ZD0205202)Anhui Provincial Natural Science Foundation(2408085Y043)National Natural Science Foundation of China(82471540,32030046,32200798)。
文摘Astrocytes are associated with varying brain size between rodents and primates.As a close evolutionary relative of primates,the tree shrew(Tupaia belangeri)provides a valuable comparative model for investigating glial architecture.However,the anatomical distribution and morphological characteristics of astrocytes in the tree shrew brain remain poorly characterized.In this study,glial fibrillary acidic protein(GFAP)immunofluorescence was employed to systematically examine the spatial distribution and morphology of astrocytes in the whole brain of tree shrews.Notably,GFAP-immunoreactive(ir)astrocytes were detected throughout the telencephalon,diencephalon,mesencephalon,metencephalon,and myelencephalon.Distinct laminar distribution was evident in regions such as the main olfactory bulb and hippocampus.Semi-quantitative comparisons revealed significant regional differences in astrocyte density between tree shrews and mice,encompassing the main olfactory bulb,accessory olfactory bulb,olfactory tubercle,cortex,hippocampus,cortical amygdaloid nucleus,hypothalamus,thalamus,superior colliculus,interpeduncular nucleus,median raphe nucleus,and parabrachial nucleus.Compared to mice,tree shrews exhibited higher astrocyte density with increased morphological complexity in the posterior hypothalamic nucleus,dorsomedial hypothalamic nucleus,ventromedial hypothalamic nucleus,and periaqueductal gray,but lower density with greater morphological complexity in the hippocampus and substantia nigra.In the paraventricular hypothalamic nucleus and lateral hypothalamic area,GFAP-ir astrocytes displayed comparable densities between tree shrews and mice but exhibited region-specific differences in morphological complexity.This study provides the first brain-wide mapping of GFAP-ir astrocytes in tree shrews,revealing marked interspecies differences in their distribution and morphology,and establishing a neuroanatomical framework for understanding astrocyte involvement in diverse physiological and behavioral functions.
文摘Over the past three decades,there has been increasing interest in miniaturized percutaneous nephrolithotomy(mPCNL)techniques featuring smaller tracts as they offer potential solutions to mitigate complications associated with standard PCNL(sPCNL).However,despite this growing acceptance and recognition of its benefits,unresolved controversies and acknowledged limitations continue to impede widespread adoption due to a lack of consensus on optimal perioperative management strategies and procedural tips and tricks.In response to these challenges,an international panel comprising experts from the International Alliance of Urolithiasis(IAU)took on the task of compiling an expert consensus document on mPCNL procedures aimed at providing urologists with a comprehensive clinical framework for practice.This endeavor involved conducting a systematic literature review to identify research gaps(RGs),which formed the foundation for developing a structured questionnaire survey.Subsequently,a two-round modified Delphi survey was implemented,culminating in a group meeting to generate final evidence-based comments.All 64 experts completed the second-round survey,resulting in a response rate of 100.0%.Fifty-eight key questions were raised focusing on mPCNLs within 4 main domains,including general information(13 questions),preoperative work-up(13 questions),procedural tips and tricks(19 questions),and postoperative evaluation and follow-up(13 questions).Additionally,9 questions evaluated the experts’experience with PCNLs.Consensus was reached on 30 questions after the second-round survey,while professional statements for the remaining 28 key questions were provided after discussion in an online panel meeting.mPCNL,characterized by a tract smaller than 18 Fr and an innovative lithotripsy technique,has firmly established itself as a viable and effective approach for managing upper urinary tract stones in both adults and pediatrics.It offers several advantages over sPCNL including reduced bleeding,fewer requirements for nephrostomy tubes,decreased pain,and shorter hospital stays.The series of detailed techniques presented here serve as a comprehensive guide for urologists,aiming to improve their procedural understanding and optimize patient outcomes.
文摘Cyclin-dependent kinase 1 （Cdkl）/cyclin B1 complex is the driving force for mitotic entry, and its activation is tightly regulated by the G2/M checkpoint. We originally reported that a novel protein C53 （also known as Cdk5rap3 and LZAP） potentiates DNA damage-induced cell death by modulating the G2/M checkpoint. More recently, Wang et al. （2007） found that C53/LZAP may function as a tumor suppressor by way of inhibiting NF-kB signaling. We re- port here the identification of C53 protein as a novel regulator of Cdkl activation. We found that knockdown of C53 protein causes delayed Cdkl activation and mitotic entry. During DNA damage response, activation of checkpoint kinase 1 and 2 （Chkl and Chk2） is partially inhibited by C53 overexpression. Intriguingly, we found that C53 inter- acts with Chkl and antagonizes its function. Moreover, a portion of C53 protein is localized at the centrosome, and centrosome-targeting C53 potently promotes local Cdkl activation. Taken together, our results strongly suggest that C53 is a novel negative regulator of checkpoint response. By counteracting Chkl, C53 promotes Cdkl activation and mitotic entry in both unperturbed cell-cycle progression and DNA damage response.
文摘The diagnosis and management of obscure gastrointestinal bleeding(OGIB) have changed dramatically since the introduction of video capsule endoscopy(VCE) followed by deep enteroscopy and other imaging technologies in the last decade. Significant advances have been made, yet there remains room for improvement in our diagnostic yield and treatment capabilities for recurrent OGIB. In this review, we will summarize the latest technologies for the diagnosis of OGIB, limitations of VCE, technological enhancement in VCE, and different management options for OGIB.
文摘Anal cancer represents less than 1% of all new cancers diagnosed annually in the United States. Yet, despite the relative paucity of cases, the incidence of anal cancer has seen a steady about 2% rise each year over the last decade. As such, all healthcare providers need to be cognizant of the evaluation and treatment of anal squamous cell carcinoma. While chemoradiation remains the mainstay of therapy for most patients with anal cancer, surgery may still be required in recurrent, recalcitrant and palliative disease. In this manuscript, we will explore the diagnosis and management of squamous cell carcinoma of the anus.
文摘Despite multiple efforts aimed at early detection through screening, colon cancer remains the third leading cause of cancer-related deaths in the United States, with an estimated 51000 deaths during 2013 alone. The goal remains to identify and remove benign neoplastic polyps prior to becoming invasive cancers. Polypoid lesions of the colon vary widely from hyperplastic, hamartomatous and inflammatory to neoplastic adenomatous growths. Although these lesions are all benign, they are common, with up to one-quarter of patients over 60 years old will develop pre-malignant adenomatous polyps. Colonoscopy is the most effective screening tool to detect polyps and colon cancer, although several studies have demonstrated missed polyp rates from 6%-29%, largely due to variations in polyp size. This number can be as high as 40%, even with advanced (> 1 cm) adenomas. Other factors including sub-optimal bowel preparation, experience of the endoscopist, and patient anatomical variations all affect the detection rate. Additional challenges in decision-making exist when dealing with more advanced, and typically larger, polyps that have traditionally required formal resection. In this brief review, we will explore the recent advances in polyp detection and therapeutic options.
基金supported in part by grants from the National Institute of Health GM89630 and AI63080an endowed Research Scholar Chair by the Medical Research Institute Councilby an internal grant of the University of Maryland Medical Center(RYZ).
文摘Progression of cells from G2 phase of the cell cycle to mitosis is a tightly regulated cellular process that requires activation of the Cdc2 kinase, which determines onset of mitosis in all eukaryotic cells. In both human and fission yeast (Schizosaccharomyces pombe) cells, the activity of Cdc2 is regulated in part by the phosphorylation status of tyrosine 15 (Tyr15) on Cdc2, which is phosphorylated by Wee1 kinase during late G2 and is rapidly dephosphorylated by the Cdc25 tyrosine phosphatase to trigger entry into mitosis. These Cdc2 regulators are the downstream targets of two well- characterized G2/M checkpoint pathways which prevent cells from entering mitosis when cellular DNA is damaged or when DNA replication is inhibited. Increasing evidence suggests that Cdc2 is also commonly targeted by viral proteins, which modulate host cell cycle machinery to benefit viral survival or replication. In this review, we describe the effect of viral protein R (Vpr) encoded by human immunodeficiency virus type 1 (HIV-1) on cell cycle G2/M regulation. Based on our current knowledge about this viral effect, we hypothesize that Vpr induces cell cycle G2 arrest through a mechanism that is to some extent different from the classic G2/M checkpoints. One the unique features distinguishing Vpr-induced G2 arrest from the classic checkpoints is the role of phosphatase 2A (PP2A) in Vpr-induced G2 arrest. Interestingly, PP2A is targeted by a number of other viral proteins including SV40 small T antigen, polyomavirus T antigen, HTLV Tax and adenovirus E4orf4. Thus an in-depth understanding of the molecular mechanisms underlying Vpr-induced G2 arrest will provide additional insights into the basic biology of cell cycle G2/M regulation and into the biological significance of this effect during host-pathogen interactions.
文摘To investigate of pediatric ulcerative colitis activity index(PUCAI)in ulcerative colitis correlate with mucosal inflammation and endoscopic assessment of disease activity(Mayo endoscopic score).METHODSWe reviewed charts from ulcerative colitis patients who had undergone both colonoscopy over 3 years.Clinical assessment of disease severity within 35 d(either before or after)the colonoscopy were included.Patients were excluded if they had significant therapeutic interventions(such as the start of corticosteroids or immunosuppressive agents)between the colonoscopy and the clinical assessment.Mayo endoscopic score of the rectum and sigmoid were done by two gastroenterologists.Inter-observer variability in Mayo score was assessed.RESULTSWe identified 99 patients(53%female,74%pancolitis)that met inclusion criteria.The indications for colonoscopy included ongoing disease activity(62%),consideration of medication change(10%),assessment of medication efficacy(14%),and cancer screening(14%).Based on PUCAI scores,33%of patients were in remission,39%had mild disease,23%had moderate disease,and 4%had severe disease.There was“moderate-substantial”agreement between the two reviewers in assessing rectal Mayo scores(kappa=0.54,95%CI:0.41-0.68).CONCLUSIONEndoscopic disease severity(Mayo score)assessed by reviewing photographs of pediatric colonoscopy has moderate inter-rater reliability,and agreement was less robust in assessing patients with mild disease activity.Endoscopic disease severity generally correlates with clinical disease severity as measured by PUCAI score.However,children with inflamed colons can have significant variation in their reported clinical symptoms.Thus,assessment of both clinical symptoms and endoscopic disease severity may be required in future clinical studies.
文摘Prosthetic joint infections(PJIs),although not very common,currently pose a very significant threat since they are associated with severe complications,high morbidity rates and substantial costs.PJIs are most commonly caused by Staphylococcus aureus and coagulase-negative staphylococci.The diagnosis of implant-associated infections is very challenging since no single routinely used laboratory or clinical test has been shown to demonstrate adequate results with respect to sensitivity,specificity and accuracy.In most cases,a sum of clinical signs and symptoms,histopathology,blood tests,radiography,bone scans and microbiological testing is considered to arrive at an accurate diagnosis.Treatment of PJIs is also very difficult since most of the infections are caused by biofilm-producing microorganisms which are significantly more resistant to the hosts natural defense mechanisms and antibiotic treatment.For successful management,a combination of both antibiotic and surgical treatment is most often required,and early diagnosis is of the utmost importance.Thus,a multidisciplinary approach is potentially the best option in dealing with PJI,and should include the involvement of microbiologists,orthopedic specialists,clinicians,pathologists and radiologists in order to improve decision-making processes and ensure overall success.The following review aims at briefly outlining the microbiology,diagnostic and treatment options,and preventive measures associated with such infections.
文摘BACKGROUND Alzheimer’s disease(AD)is among the most prevalent forms of dementia in the world and neuropathological studies suggest similar high prevalence of mixed(AD+vascular)dementias.Approximately 25%-50%of individuals with AD develop psychosis sometime during their illness.The presence of psychosis in AD worsens outcomes.Currently there are no United States Food and Drug Administration(FDA)approved medications for the treatment of psychosis in AD.Pimavanserin,a novel atypical antipsychotic medication,was approved by the FDA for the treatment of hallucinations and delusions associated with Parkinson disease psychosis and is currently in clinical trials for the treatment of psychosis in AD.AIM To evaluate the existing literature regarding the use of pimavanserin for treating psychosis among individuals with AD.METHODS A literature review of clinical studies of pimavanserin treatment for psychosis in individuals with AD was performed using the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines.Trials were identified by systematically searching PubMed,MEDLINE,EMBASE,Cochrane Central Register of Controlled Trials,Web of Science,and Scopus through October 2019.The 5-point Jadad scoring system was used to assess the methodologic quality of the randomized placebo-controlled trials.RESULTS A total of 499 citations were retrieved and pooled in EndNote and de-duplicated to 258 citations.This set was uploaded to Covidence for screening.Two separate screeners(Srinivasan S and Tampi RR)evaluated the titles,abstracts,and full text of eligible articles.Of the identified 258 abstracts,98 articles underwent full text review and 2 publications from 1 randomized controlled trial(RCT)were included in the final analysis.The quality of evidence was assessed to be of good methodologic quality,scoring 4 out of 5 using the 5-point Jadad questionnaire with the Jadad Scoring calculation.This systematic review found only one RCT that evaluated the use of pimavanserin for the treatment of psychosis among individuals with AD.This phase 2 trial resulted in two publications,the second of which was a subgroup analysis from the original study.The evidence from these two publications showed that pimavanserin improves psychotic symptoms among individuals with AD when compared to placebo at week 6.CONCLUSION Pimavanserin may be a pharmacologic consideration for the treatment for psychosis in AD.Additional RCTs are needed to assess the evidence of effectiveness before pimavanserin is considered a standard treatment.
基金Supported by Grand-in-aid for Science Research from the Japanese Ministry of Education,Culture,Sports,Science and Technology,No.26861063
文摘Hepatitis C is a strong prognostic factor for patients with hepatocellular carcinoma(HCC). Although liver resection and liver transplantation offer the chance of a cure for HCC,adequate management of co-existing infection with hepatitis C virus(HCV) is important to enable better long-term outcomes after surgery for HCV-related HCC. For patients undergoing liver resection,perioperative anti-viral treatment is recommended,since a decreased HCV viral load itself is reportedly associated with a lower tumor recurrence rate and a longer overall survival. For patients undergoing transplanatations for HCC complicated by end-stage liver disease,the post-transplant management of HCV infection is also necessary to prevent progressive graft injury caused by active hepatitis under the immunosuppressive condition that is needed after liver transplantation. Although only a few lines of solid evidence are available for postoperative antiviral treatment because of the limited indication and frequent adverse events caused by conventional high-dose combination interferon therapy,new direct acting anti-viral agents would enable interferon-free anti-viral treatment with a higher virologic response and minimal side effects.
