Clostridium difficile infection following colon subtotal resection in a patient with gallstones: A case report and review of literature

BACKGROUND Clostridium difficile(C.difficile)infection(CDI)is a rare clinical disease caused by changes in the intestinal microenvironment,which has a variety of causes and a poor prognosis,and for which there is no standardized clinical treatment.CASE SUMMARY A patient experienced recurrent difficulty in bowel movements over the past decade.Recently,symptoms worsened within the last ten days,leading to a clinic visit due to constipation.The patient was subsequently referred to our depart-ment.Preoperatively,the patient was diagnosed with obstructed colon accom-panied by gallstones.Empirical antibiotics were administered both before and after surgery to prevent infection.On the fourth day post-surgery,symptoms of CDI emerged.Stool cultures confirmed the presence of C.difficile DNA.Treatment involved a combination of vancomycin and linezolid,resulting in the patient's successful recovery upon discharge.However,the patient failed to adhere to the prescribed medication after discharge and was discovered deceased during a follow-up two months later.CONCLUSION CDI is the leading cause of nosocomial post-operative care,with limited clinical cases and poor patient prognosis,and comprehensive clinical treatment guidelines are still lacking.This infection can be triggered by a variety of factors,including intestinal hypoxia,inappropriate antibiotic use,and bile acid circulation disorders.In patients with chronic bowel disease and related etiologies,prompt preoperative attention to possible CDI and preoperative bowel preparation is critical.Adequate and prolonged medication should be maintained in the treatment of CDI to prevent recurrence of the disease.

Surgery and follow-up care for auricular keloid:a report of 156 cases

Objective:To treat and prevent auricular keloid so as to imporve the cure rate and lower the rate of recurrence. Methods:Taking 156 sufferers of auriclar keloid at the orthopaedics department of the Southwest Hospital under the Third Military Medical University from June, 2008 to June, 2011 as the research subject, this research carried out retrospective analysis and summary of different surgical methods with the clinical data of subseque nt treatments, including medicament, radiotheropy, pressure, etc. Results:There was no auricular cartilage necrosis and deformation in the total of 156 cases. It was found that 134 cases were cured in a year of postoperative follow-up, getting the care rate to 85.9%. The treatment was effective on 20 cases, with the effective rate of 12.8%, while it was ineffective on 2 cases, with the ineffective rate being 1.3%. However, two cases showed tendency towards recurrence, which were treated effectively by non-surgical methods like local hormone injection. There was neither recurrence nor apparent hyperplasia of hypertrophic scars on the rest cases, with the auricle and the earlobe in good shape. Conclusion:By auricular keloid excision and stripping surgery, surgical suture tension was reduced. Glucocorticoid and radiotherapy were instantly applied to inhibit pyperplasia of cicatrical tissue. Subsequently, pressure, anti-scarring drugs and silicone membrane were adopted to ensure fine postoperative apperance and reduce recurrence. These methods were proved to be effectiveand they provided systematic and effective treatment for auricular keloid.

Preliminary Clinical Study Using a Novel Wound Dressing Composed of Hyaluronic Acid and Collagen Containing EGF

This clinical trial aimed to evaluate the efficacy and safety of a novel wound dressing composed of hyaluronic acid (HA) and collagen (Col) containing epidermal growth factor (EGF), referred to as EGF-wound dressing. EGF-wound dressing was prepared by freeze-drying a mixed aqueous solution of high-molecular-weight HA, low-molecular-weight HA and heat-denatured Col containing EGF. EGF-wound dressing was applied to skin defects, such as intractable skin ulcers, burn ulcers, traumatic skin defects and skin donor-site wounds. The dressing was changed twice a week for a period of 6 weeks or longer, if necessary. The primary endpoints were size of wound area, formation of granulation tissue, extent of epithelialization, infection control and macroscopic appearance. Effectiveness, safety and overall clinical evaluation were scored by plastic surgeons, as authorized by the Japanese Society of Plastic and Reconstructive Surgery. This study was registered with the University Hospital Medical Information Network (UMIN0000005264). Healthy granulation tissue and rapid epithelialization were observed for a given period after application of EGF-wound dressing onto the wounds. Most cases were assessed as having achieved good or excellent results. This clinical study demonstrated that EGF-wound dressing was beneficial in the treatment of various skin defects.

Treatment of mild and moderate congenital ptosis via the levator imbrication technique

Background:To correct mild and moderate congenital ptosis,traditional surgical techniques usually include dissection of the Müller’s muscle.Meanwhile,both the levator palpebrae superioris and the Müller’s muscle play a synergistic role to elevate the upper eyelid.Thus,to protect the Müller muscle and minimize injury,we developed and applied a levator imbrication technique in patients with mild and moderate congenital ptosis and followed it up to evaluate its clinical efficacy.Methods:This retrospective case series included 53 patients with mild and moderate congenital ptosis,all of whom had undergone ptosis correction using the levator imbrication technique at the Plastic and Aesthetic Department of the Second Affiliated Hospital of Zhengzhou University between June 2018 and June 2020.The outcomes of correction,upper eyelid appearance,and operative complications were observed and analyzed.The postoperative follow-up was 3–12 months.Results:Fifty cases of ptosis were fully corrected,and the bilateral double eyelids were smooth and natural.The eyelids of 20 patients were incompletely closed immediately after the operation but were able to close spontaneously within 2 weeks.No serious complications such as exposure keratitis were reported.Three patients with undercorrection underwent reoperation 3 months after the first operation,and ptosis was corrected.Conclusion:The levator imbrication technique for mild and moderate congenital ptosis is simple to perform and shortens the operation time with less damage,stable postoperative outcomes,and no long-term complications.

Effects of connective tissue growth factor antisense oligonucleotides on the proliferation and collagen synthesis of the cultured human keloid fibroblasts in vitro

Objective: To explore the effects of connective tissue growth factor (CTGF) on the pathogenesis of human keloid. Methods: CTGF antisense oligonucleotides (ASODN) conjugated with isothiocyananate fluorescence was encapsulated by liposome, and then added into the human keloid fibroblasts (HKFs) culture media. The intracellular distribution of CTGF ASODN was observed by fluorescence microscopy in the fixed HKFs. The proliferation of HKFs was measured by MTT test. The collagen synthesis of HKFs was measured by 3H-proline incorporation method. Results: Compared with control group, the CTGF ASODN can inhibit the proliferation and collagen synthesis of the HKFs (P<0.01). Conclusion: CTGF ASODN has anti-fibrotic effects on keloid in vitro, and CTGF play an important role in promoting the fibrosis of keloid.

An extract of Hypericum perforatum induces wound healing through inhibitions of Ca^(2+) mobilizations,mitochondrial oxidative stress and cell death in epithelial cells:Involvement of TRPM2 channels

The wound is induced by several mechanical and metabolic factors.In the etiology of the wound recovery,excessive oxidative stress,calcium ion(Ca^(2+))influx,and apoptosis have important roles.Ca^(2+)-permeable TRPM2 channel is activated by oxidative stress.Protective roles of Hypericum perforatum extract(HP)on the mechanical nerve injury-induced apoptosis and oxidative toxicity through regulation of TRPM2 in the experimental animals were recently reported.The potential protective roles in HP treatment were evaluated on the TRPM2-mediated cellular oxidative toxicity in the renal epithelium(MPK)cells.The cells were divided into three groups as control,wound,and wound+HP treatment(75μM for 72 h).Wound diameters were more importantly decreased in the wound+HP group than in the wound group.In addition,the results of laser confocal microscopy analyses indicated protective roles of HP and TRPM2 antagonists(N-(p-Amylcinnamoyl)anthranilic acid and 2-aminoethyl diphenylborinate)against the wound-induced increase of Ca^(2+) influx and mitochondrial ROS production.The wound-induced increase of early(annexin V-FITC)apoptosis and late(propidium iodide)apoptosis were also decreased in the cells by the HP treatment.In conclusion,HP treatment acted protective effects against wound-mediated oxidative cell toxicity and apoptosis through TRPM2 inhibition.These effects may be attributed to their potent antioxidant effect.

A selective inhibitor of OMA1 and targeted delivery system for the treatment of acute myocardial infarction

The rescue of dying cardiomyocytes in penumbra within 4 hours is the best way to preserve cardiac function in acute myocardial infarction(AMI).Mitochondrial fission contributes to mitochondrial energy supply deficiency and cardiomyocytes death,and OMA1 promotes mitochondrial fission.Accurate targeting of OMA1 inhibition is important for the treatment of myocardial infarction.Here,a selective inhibitor of OMA1,UNC-R,was firstly described,which could protect the cardiomyocytes through mitochondrial fission inhibition.Moreover,the accurately targeted microsphere was designed,and loaded the UNC-R to form the POMU,which could avoid the phagocytosis of phagocytes in blood,precisely accumulated in the ischemic area,further target the dying cardiomyocytes.

Combined Therapy for Mandibular Prognathism:Sagittal Split Osteotomy with Excision of Tongue

In the evaluation of the beauty and functional integrity of the lower face, the oral cavity, teeth, mandible, maxilla, and the size and position of the tongue are important. The tongue locates forward and is larger than normal in prognathism, in which the jaw protrudes from the skull. It is not clear whether an enlarged tongue causes the open bite, protrusion or dental arch misalignment, or is a result of them. Here, we report two patients with mandibular prognathism and relative macroglossia, which were treated by mandibular setback surgery using a bilateral sagittal split osteotomy (BSSO) and excision of the tongue. This procedure achieved aesthetic improvement of the face and dentition.

Research on combination of PRP,PRF and adipose-derived stem cells for wound healing of chronic skin ulcer

Objective To investigate the effects of combination of PRP,PRF and adipose-derived stem cells(ADSC)for wound healing of chronic skin ulcer,and provide evidences for clinical application.Methods Twenty-four SD rats aged 6-8 weeks were used in this study.5 grams of groin adipose tissue were derived from each rat.After collagenase digestion,mesenchyma stem cells derived from adipose tissue(ADSCs)were determined by immunocytochemical method and flow cytometry.After continuous culturing,the 3th passage of ADSCs in good condition was prepared for transplantation.Ten milliliters of whole blood were extracted from one rat for making PRP and PRF backup.Full thickness skin defect model with six wounds with an area of 1.5cm*1.5cm on each side of the spine on the back was established in rats after anesthesia.Then the rats were randomly divided into six groups.Skin wounds were injected with PRF combining ADSC in group A,PRF in group B,ADSC in group C,ADSC combining PRP in group D,PRP in group E,and same amount of normal saline(NS)in group F.Histological analysis was performed to evaluate the velocity and the quality of the wound healing 7 days,14 days,21days and 28 days after treatment,and comparing the regeneration of epidermis,corium,fibroblast,blood vessel and skin appendages respectively.Results The woulds in each group healed well,without symptoms of infection.Skin wounds were almost healed in 21 days,and no significant difference in healing velocity was found among these groups.There were no apparent inflammatory cells in 7 days.The wounds were filled with granulation formed by proliferation of connective tissue with visible new blood capillary and repair cells like fibroblast.Epidermis grew out and became thick,and gradually grew to the wounds,with active proliferation of re-epithelization.Re-epithelization was completed in 14 days,with granulation tissue covered by epidermis and fibrosis showing a significant increase in collagenous fiber,and visible skin appendages like new hair follicle,glandula sebacea,sweat gland and corneum.Appendages like hair follicle,glandula sebacea,sweat gland and corneum increased in 21 days,and granulation tissue gradually formed scar tissue and entered remodeling phase.There was no significant changes from 21 days to 28 days,and the tissues were entering a long remodeling phase.Healing status:Group D,A and C could be observed with more complete epidermis,new blood vessel and new hair follicle.Among them,Group D was most significant,while group A,C,E,B successively and group F had the slowest epidermal migration and the least new hair follicle.The velocity and the quality of these groups were as follows:D>A>C>E>B>F,indicating that ADSC combining PRP can improve quality in wound healing of skin ulcer effectively.Conclusions After the general and pathological observation on the effects,the velocity and the quality for the skin ulcer healing of SD rats on the back were as follows:ADSC+PRP>ADSC+PRF>ADSC>PRP>PRF>NS,indicating that PRP or PRF combining ADSC can improve quality in wound healing of skin ulcer effectively.

Transplantation of human induced pluripotent stem cell derived keratinocytes accelerates deep second-degree burn wound healing

BACKGROUND Current evidence shows that human induced pluripotent stem cells(hiPSCs)can effectively differentiate into keratinocytes(KCs),but its effect on skin burn healing has not been reported.AIM To observe the effects of hiPSCs-derived KCs transplantation on skin burn healing in mice and to preliminarily reveal the underlying mechanisms.METHODS An analysis of differentially expressed genes in burn wounds based on GEO datasets GSE140926,and GSE27186 was established.A differentiation medium containing retinoic acid and bone morphogenetic protein 4 was applied to induce hiPSCs to differentiate into KCs.The expression of KCs marker proteins was detected using immunofluorescence staining.A model of a C57BL/6 mouse with deep cutaneous second-degree burn was created,and then phosphate buffered saline(PBS),hiPSCs-KCs,or hiPSCs-KCs with knockdown of COL7A1 were injected around the wound surface.The wound healing,re-epithelialization,engraftment of hiPSCs-KCs into wounds,proinflammatory factor level,and the NF-κB pathway proteins were assessed by hematoxylin-eosin staining,carboxifluorescein diacetate succinimidyl ester(CFSE)fluorescence staining,enzyme linked immunosorbent assay,and Western blotting on days 3,7,and 14 after the injection,respectively.Moreover,the effects of COL7A1 knockdown on the proliferation and migration of hiPSCs-KCs were confirmed by immunohistochemistry,EdU,Transwell,and damage repair assays.RESULTS HiPSCs-KCs could express the hallmark proteins of KCs.COL7A1 was down-regulated in burn wound tissues and highly expressed in hiPSCs-KCs.Transplantation of hiPSCs-KCs into mice with burn wounds resulted in a significant decrease in wound area,an increase in wound re-epithelialization,a decrease in proinflammatory factors content,and an inhibition of NF-κB pathway activation compared to the PBS group.The in vitro assay showed that COL7A1 knockdown could rescue the inhibition of hiPSCs-KCs proliferation and migration,providing further evidence that COL7A1 speeds up burn wound healing by limiting cell proliferation and migration.CONCLUSION In deep,second-degree burn wounds,COL7A1 can promote KC proliferation and migration while also suppressing the inflammatory response.

Lateral Crus Graft with Autologous Rib Cartilage for Cleft Lip Nostril Asymmetry: A Report of 35 Cases

Summary： A surgical technique of lateral crus strut graft to correct the deformity of nostril contour and improve asymmetric nostril shape by autologous rib cartilage was reported. Thirty-five patients （20 males and 15 females）, with a mean age of 19 years （range of 16-26 years） were included in this study. All of the patients suffered moderate to severe unilateral cleft lip nostril deformity and underwent surgical technique of lateral crus strut graft by autologous rib cartilage to correct the asymmetric nostril contour from 2010 to 2012. The views of the nostril contour on both sides were reviewed and some parameters were measured at different time points （preoperatively, and 3 months and one year postoperatively） including the long axis and short axis of the nostrils. The differences in nostrils including long axis, short axis, elliptical area and eccentricity on the both sides were compared at different time points. The differences in the long axis and eccentricity of the nostrils on the two sides were decreased significantly between the preoperative view and postoperative view （P〈0.05）. The surgical technique of lateral crus graft with autologous rib cartilage is effective to correct the abnormal nostril contour and improve the asymmetry for unilateral cleft clip patients.

Misdiagnosis of scalp angiosarcoma: A case report

BACKGROUND Angiosarcoma is a rare malignant tumor.Owing to the lack of specific clinical manifestations of this disease,it is difficult to achieve early diagnosis and start early treatment.CASE SUMMARY A 78-year-old male patient was admitted to the hospital because of a bump on his head that did not heal for 4 mo.The patient was diagnosed with a refractory head wound.The patient underwent neoplasm resection and skin grafting surgery in the Plastic Surgery.The neoplasm was sent for pathological examination during the operation.The final pathological results were confirmed scalp angiosarcoma.CONCLUSION Our research suggests that pathological examination should be performed for refractory ulcers of the scalp,and physical factor therapy should be used with caution before the diagnosis is clear.

Anti-ageing effects of a new Dimethylaminoethanol-based formulation on DGalactose induced skin ageing model of rat

Background Dimethylaminoethanol has been widely used to fight against wrinkles, in the field of aesthetic medicine there is an increasing demand for safe and effective Dimethylaminoethanol-based products to counteract the ageing process. Objective To evaluate the anti- ageing effects of a new DMAE- based formulation. Methods 30 male rats were randomly allocated into treatment,D-gal ageing modeland control groups, each of which contained ten rats.Treatment group and D- gal ageing model group were subcutaneously injected with D- galactose prepared in normal saline 125mg·kg-1·d-1for 42 d. Control groups were injected with normal saline for42 d with same method and dose. From the 18 th day,after shaving their hair,the treatment grouprats were injected thisnew DMAE-based formulation at a dose of 1ml per week for 4 weeks in the Dermis of two sides hip skin mark zone.Meanwhile,D-gal ageing model group rats were administrated the same volume of normal saline with same method. Skin specimens were obtained 3days after the last treatment. Dermal collagen density and dermal thickness were evaluated by H&E and Massontrichrome staining. And m RNA expressions of TGFβ1, Smad3, Type I,Type III Pro-collagen,TIMP-1,MMP- 1,were assessed by Real- time quantitative polymerase chain reaction. Results Dermal thickness, dermal collagen density and hydroxyproline content in treatment group increased significantly comparing with D- gal ageing model group. No differences were found in m RNA expression of MMP- 1 and Type III Pro- collagen between the treatment group and D- gal ageing model group. In addition, m RNA expression of TGFβ1, Type I Pre-collagen, TIMP1 and smad3 in treatment group were significantly up- regulated in contrast with D- gal ageing model and control group. Conclusion This new DMAE- based formulationcould generate anti- ageing effects by activating collagen synthesisthrough TGF-β1/Smads signaling pathway.

Inhibitory Effect of Photodynamic Therapy on Keloids

Objective To investigate the inhibitory effect of photodynamic on keloid by observing the changes of various indicators of keloid under the action of different concentration of photosensitizer aminoketovaleric acid combined with laser.Methods Fifteen healthy nude mice were randomly divided into experimental group 1,experimental group 2 and control group.Keloid tissue was implanted into the back to form stable pathological scars.10%aminoketovaleric acid solution,20%aminoketovaleric acid solution,saline solution were applied to the back of the nude mice within 4,8 and 12 weeks,respectively,for half an hour,635 nm CW laser irradiation,and scar tissue was cut at 6,10 and 14 weeks for detection.Scar related indicators.Results Scar index,number of fibroblasts,number of TGF-beta 1 protein and alpha-SMA in the experimental group were lower than those in the control group,and more than 2 indexes in the experimental group were lower than those in the experimental group 1.There was significant difference among the groups.Conclusion 20%aminoketovaleric acid can produce cytotoxic effect,induce apoptosis of fibroblasts,regulate and reduce epithelial-mesenchymal transition of scar,and inhibit keloid.

Construction of tissue-engineered vascular grafts with enhanced patency by integrating heparin,cell-adhesive peptide,and carbon monoxide nanogenerators into acellular blood vessels

Small-diameter tissue-engineered vascular grafts(sdTEVGs)have garnered significant attention as a potential treatment modality for vascular bypass grafting and replacement therapy.However,the intimal hyperplasia and thrombosis are two major complications that impair graft patency during transplantation.To address this issue,we fabricated the covalent-organic framework(COF)-based carbon monoxide(CO)nanogenerator-and co-immobilized with LXW-7 peptide and heparin to establish a multifunctional surface on TEVGs constructed from acellular blood vessels for preventing thrombosis and stenosis.The cell-adhesive peptide LXW-7 could capture endothelial-forming cells(EFCs)to promote endothelialization,while the antithrombotic molecule heparin prevented thrombus formation.The reactive oxygen species(ROS)-triggered CO release suppressed the adhesion and activation of macrophages,leading to the reduction of ROS and inflammatory factors.As a result,the endothelial-to-mesenchymal transition(EndMT)triggered by inflammation was restricted,facilitating the maintenance of the homeostasis of the neo-endothelium and preventing pathological remodeling in TEVGs.When transplanted in vivo,these vascular grafts exhibited negligible intimal hyperplasia and remained patent for 3 months.This achievement provided a novel approach for constructing antithrombotic and anti-hyperplastic TEVGs.

Recent progress and clinical applications of advanced biomaterials in cosmetic surgery

Materials of different allogeneic or xenogeneic or autologous origins are widely used as soft-tissue fillers or structural scaffolds in the field of cosmetic surgery,while complications including prosthesis infection,donor site deformity and filler embolization have always been difficult problems for plastic surgeons.The application of novel biomaterials may bring in hopeful solutions for these problems.Recently,some advanced biomaterials,such as regenerative biomaterials can effectively promote the repair of defective tissues,which have been proven to have good therapeutic as well as cosmetic effects in cosmetic surgery.Therefore,biomaterials with active compounds have drawn significant attention for the tissue regeneration of reconstructive and esthetic treatment.Some of these applications have achieved better clinical outcomes than traditional biological materials.This review summarized recent progress and clinical applications of advanced biomaterials in cosmetic surgery.

Infection control in severely burned patients

In the last two decades, much progress has been made in the control of burn wound infection and nasocomial infections(NI) in severely burned patients. The continiually changing epidemiology is partially related to greater understanding of and improved techniques for burn patient management as well as effective hospital infection control measures. With the advent of antimicrobial chemotherapeutic agents, infection of the wound site is now not as common as, for example, urinary and blood stream infections. Universal application of early excision of burned tissues has made a substantial improvement in the control of wound-related infections in burns. Additionally, the development of new technologies in wound care have helped to decrease morbidity and mortality in severe burn victims. Many examples can be given of the successful control of wound infection, such as the application of an appropriate antibiotic solution to invasive wound infection sites with simultaneous vacuum-assisted closure, optimal preservation of viable tissues with waterjet debridement systems, edema and exudate controlling dressings impregnated with Ag(Silvercel, Aquacell-Ag). The burned patient is at high risk for NI. Invasive interventions including intravenous and urinary chateterization, and entubation pose a further risk of NIs. The use of newly designed antimicrobial impregnated chateters or silicone devices may help thecontrol of infection in these immunocomprimised patients. Strict infection control practices(physical isolation in a private room, use of gloves and gowns during patient contact) and appropriate empirical antimicrobial therapy guided by laboratory surveillance culture as well as routine microbial burn wound culture are essential to help reduce the incidance of infections due to antibiotic resistant microorganisms.

Intralesional injection treatment of hypertrophic scars and keloids:a systematic review regarding outcomes

Background:The aim of this review was to explore the existing body of literature focusing on the intralesional treatments of keloids and hypertrophic scars.Methods:A comprehensive systematic review of related articles was conducted across multiple databases.Article selection was limited to those published in the English language between 1950 and 2014.Search terms for the on-line research were"scar(s),""keloid(s),""hypertrophic,""injection,""intralesional,"and"treatment".Results:The initial search returned 2548 published articles.After full text review,the final search yielded 11 articles that met inclusion criteria.A total of 14 patient samples in 11 articles were collected.The most frequent intralesional injection treatment studied was triamcinolone(n=5),fol owed by bleomycin(n=3),5-fluorouracil(n=2),verapamil(n=2),cryosurgery,and collagenase.The scar height reduction for all but one study was demonstrated,with acceptable complication and recurrence rate.Only three articles reported a follow-up period longer than 18 months,and only two studies used standardized outcome criteria with a quantitative scale.Conclusions:Although many treatment options have already been described in the literature,there is no universal y accepted treatment resulting in permanent hypertrophic or keloid scar ablation.The lack of adequately long-term powered randomized control ed trials does not permit to establish definitive conclusions with implications for routine clinical practice.Level of

Hyperbaric oxygen therapy for skin flap blood flow disorder: a case report

A female patient at the age of 17 received dilator implant on the right part of her face to prepare skin flap for her facial scar.The skin flap was in good conditions before scar cutting,but showed poor blood circulation after being transferred.Hyperbaric oxygen therapy was given at 0.2 MPa(2ATA) in double pure oxygen cabins for 90 min every day for 10 d.The skin flap showed in sound viability and sound blood circulation after the treatment.Hyperbaric oxygen therapy can be used to treat blood circulation disorder in transferred skin flap.

Electric Field:A Key Signal in Wound Healing

Wound healing is a complex biological process that involves proliferation,migration,and differentiation.Endogenous electric field(EF)-directed migration of keratinocytes(galvanotaxis)is an essential step in wound re-epithelialization.Endogenous EFs are generated instantaneously after an injury because of the collapse of transepithelial potentials.The application of exogenous EF has become increasingly widespread in promoting wound healing,leading to a paradigm shift in patient outcomes.Here,we summarize the role and value of EF in wound healing through a review of the current research.